Review



il4 r d systems  (R&D Systems)


Bioz Verified Symbol R&D Systems is a verified supplier
Bioz Manufacturer Symbol R&D Systems manufactures this product  
  • Logo
  • About
  • News
  • Press Release
  • Team
  • Advisors
  • Partners
  • Contact
  • Bioz Stars
  • Bioz vStars
  • 93

    Structured Review

    R&D Systems il4 r d systems
    Il4 R D Systems, supplied by R&D Systems, used in various techniques. Bioz Stars score: 93/100, based on 210 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/il4 r d systems/product/R&D Systems
    Average 93 stars, based on 210 article reviews
    il4 r d systems - by Bioz Stars, 2026-04
    93/100 stars

    Images



    Similar Products

    95
    MedChemExpress d recombinant rat il4
    D Recombinant Rat Il4, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 95/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/d recombinant rat il4/product/MedChemExpress
    Average 95 stars, based on 1 article reviews
    d recombinant rat il4 - by Bioz Stars, 2026-04
    95/100 stars
      Buy from Supplier

    93
    R&D Systems il4 r d systems
    Il4 R D Systems, supplied by R&D Systems, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/il4 r d systems/product/R&D Systems
    Average 93 stars, based on 1 article reviews
    il4 r d systems - by Bioz Stars, 2026-04
    93/100 stars
      Buy from Supplier

    90
    Beyotime recombinant rat il4
    Recombinant Rat Il4, supplied by Beyotime, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/recombinant rat il4/product/Beyotime
    Average 90 stars, based on 1 article reviews
    recombinant rat il4 - by Bioz Stars, 2026-04
    90/100 stars
      Buy from Supplier

    90
    R&D Systems recombinant rat il4 (ril4)
    Recombinant Rat Il4 (Ril4), supplied by R&D Systems, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/recombinant rat il4 (ril4)/product/R&D Systems
    Average 90 stars, based on 1 article reviews
    recombinant rat il4 (ril4) - by Bioz Stars, 2026-04
    90/100 stars
      Buy from Supplier

    90
    Beyotime recombinant rat il4 cat# p6267
    Recombinant Rat Il4 Cat# P6267, supplied by Beyotime, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/recombinant rat il4 cat# p6267/product/Beyotime
    Average 90 stars, based on 1 article reviews
    recombinant rat il4 cat# p6267 - by Bioz Stars, 2026-04
    90/100 stars
      Buy from Supplier

    90
    PeproTech recombinant rat interleukin-4 (il4
    HCN channel and KCNQ/Kv7 channel expression on primary microglia. #p < 0.05, ##p < 0.01, ###p < 0.001 compared different experimental groups as marked by horizontal bar. a A representative image of primary microglia culture shows purity by staining of Iba1 (red). Hoechst stains all cell nuclei blue. Images were obtained with a fluorescence microscope, scale bars = 100 μm. b Expression of microglia marker Iba1 and P2RY12. Expression of microglial ion channels KCNK13, the HCN-subunits HCN1, HCN2, HCN3, and HCN4, as well as the KCNQ/Kv7 channel subunits KCNQ2, 3, and 5, on primary rat microglia in vitro measured by RT-qPCR. Microglia were untreated, activated with LPS (10 ng/ml) or <t>IL4</t> (50 ng/ml; for Iba1: F(2, 6) = 23.571, p = 0.001, ω = 0.913; for P2YR12. F(2, 6) = 31.897, p = 0.001, ω = 0.934; for HCN2: F(2, 18) = 113.981, p < 0.0001, ω = 0.956; for HCN3: F(2, 8) = 22.573, p = 0.001, ω = 0.892; for KCNQ3: F(2, 11) = 11.674, p = 0.002, ω = 0.777; for KCNQ5: H (2) = 9.168, p = 0.01)
    Recombinant Rat Interleukin 4 (Il4, supplied by PeproTech, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/recombinant rat interleukin-4 (il4/product/PeproTech
    Average 90 stars, based on 1 article reviews
    recombinant rat interleukin-4 (il4 - by Bioz Stars, 2026-04
    90/100 stars
      Buy from Supplier

    90
    R&D Systems recombinant rat il4 (ril4
    Primer Specifications.
    Recombinant Rat Il4 (Ril4, supplied by R&D Systems, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/recombinant rat il4 (ril4/product/R&D Systems
    Average 90 stars, based on 1 article reviews
    recombinant rat il4 (ril4 - by Bioz Stars, 2026-04
    90/100 stars
      Buy from Supplier

    94
    R&D Systems recombinant rat il4
    Schematic Illustration of Preparation of <t>IL4-Loaded</t> NHG-MSa
    Recombinant Rat Il4, supplied by R&D Systems, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/recombinant rat il4/product/R&D Systems
    Average 94 stars, based on 1 article reviews
    recombinant rat il4 - by Bioz Stars, 2026-04
    94/100 stars
      Buy from Supplier

    Image Search Results


    HCN channel and KCNQ/Kv7 channel expression on primary microglia. #p < 0.05, ##p < 0.01, ###p < 0.001 compared different experimental groups as marked by horizontal bar. a A representative image of primary microglia culture shows purity by staining of Iba1 (red). Hoechst stains all cell nuclei blue. Images were obtained with a fluorescence microscope, scale bars = 100 μm. b Expression of microglia marker Iba1 and P2RY12. Expression of microglial ion channels KCNK13, the HCN-subunits HCN1, HCN2, HCN3, and HCN4, as well as the KCNQ/Kv7 channel subunits KCNQ2, 3, and 5, on primary rat microglia in vitro measured by RT-qPCR. Microglia were untreated, activated with LPS (10 ng/ml) or IL4 (50 ng/ml; for Iba1: F(2, 6) = 23.571, p = 0.001, ω = 0.913; for P2YR12. F(2, 6) = 31.897, p = 0.001, ω = 0.934; for HCN2: F(2, 18) = 113.981, p < 0.0001, ω = 0.956; for HCN3: F(2, 8) = 22.573, p = 0.001, ω = 0.892; for KCNQ3: F(2, 11) = 11.674, p = 0.002, ω = 0.777; for KCNQ5: H (2) = 9.168, p = 0.01)

    Journal: Journal of Neuroinflammation

    Article Title: The impact of hyperpolarization-activated cyclic nucleotide-gated (HCN) and voltage-gated potassium KCNQ/Kv7 channels on primary microglia function

    doi: 10.1186/s12974-020-01779-4

    Figure Lengend Snippet: HCN channel and KCNQ/Kv7 channel expression on primary microglia. #p < 0.05, ##p < 0.01, ###p < 0.001 compared different experimental groups as marked by horizontal bar. a A representative image of primary microglia culture shows purity by staining of Iba1 (red). Hoechst stains all cell nuclei blue. Images were obtained with a fluorescence microscope, scale bars = 100 μm. b Expression of microglia marker Iba1 and P2RY12. Expression of microglial ion channels KCNK13, the HCN-subunits HCN1, HCN2, HCN3, and HCN4, as well as the KCNQ/Kv7 channel subunits KCNQ2, 3, and 5, on primary rat microglia in vitro measured by RT-qPCR. Microglia were untreated, activated with LPS (10 ng/ml) or IL4 (50 ng/ml; for Iba1: F(2, 6) = 23.571, p = 0.001, ω = 0.913; for P2YR12. F(2, 6) = 31.897, p = 0.001, ω = 0.934; for HCN2: F(2, 18) = 113.981, p < 0.0001, ω = 0.956; for HCN3: F(2, 8) = 22.573, p = 0.001, ω = 0.892; for KCNQ3: F(2, 11) = 11.674, p = 0.002, ω = 0.777; for KCNQ5: H (2) = 9.168, p = 0.01)

    Article Snippet: Microglia were left unstimulated (control) or were stimulated with 10 ng/ml lipopolysaccharide (LPS derived from E. coli 0111: B4, Sigma Aldrich, St. Louis, USA) to activate microglia towards a pro-inflammatory phenotype, or alternatively stimulated with 50 ng/ml recombinant rat interleukin-4 (IL4; Peprotech, Hamburg, Germany) to polarize microglia to an anti-inflammatory phenotype [ ].

    Techniques: Expressing, Staining, Fluorescence, Microscopy, Marker, In Vitro, Quantitative RT-PCR

    Activation characteristics of primary microglia. * p < 0.05; ** p < 0.01; *** p < 0.001 compared to different experimental groups as marked by a horizontal bar. Characterization of the activated pro-inflammatory microglia phenotype by the expression of the inducible nitric oxide (NO) synthetase (iNOS) and release of NO after blockade of HCN and KCNQ/Kv7 channels with ZD7288 and XE-991 (30 μM each), respectively. Treatment with LPS (10 ng/ml) served as a positive control. a . iNOS expression was measured on RNA level by RT-qPCR (H(3) = 11.608, p < 0.009) and on b protein level by immunocytochemistry (H(3) = 17.665, p = 0.001). c Release of NO was measured by Griess assay (μmol/l; H(3) = 15.784, p = 0.001). Characterization of the anti-inflammatory phenotype of activated microglia by expression of CD206, release of insulin-like growth factor 1 (IGF1), and change of phagocytic capacity, after pharmacological block of HCN and KCNQ/Kv7 channels by 30 μM ZD7288 and XE-991, respectively. Treatment with IL4 (25 ng/ml) served as a positive control. d Regulation of CD206 expression on RNA level was measured by RT-qPCR (F (3, 20) = 13.981, p < 0.0001, ω = 0.62). e IGF1 release was measured by ELISA (pg/ml, H(3) = 15.805, p = 0.001). f Zymosan engulfment showed phagocytic activity of microglia (H(3) = 11.653, p < 0.009). Data were blank-corrected and normalized to control. g Representative immunocytochemical stainings for the microglia marker Iba1 (red), co-stained for iNOS (green), and Hoechst as a nuclear counterstain (blue); scale bars = 50 μm

    Journal: Journal of Neuroinflammation

    Article Title: The impact of hyperpolarization-activated cyclic nucleotide-gated (HCN) and voltage-gated potassium KCNQ/Kv7 channels on primary microglia function

    doi: 10.1186/s12974-020-01779-4

    Figure Lengend Snippet: Activation characteristics of primary microglia. * p < 0.05; ** p < 0.01; *** p < 0.001 compared to different experimental groups as marked by a horizontal bar. Characterization of the activated pro-inflammatory microglia phenotype by the expression of the inducible nitric oxide (NO) synthetase (iNOS) and release of NO after blockade of HCN and KCNQ/Kv7 channels with ZD7288 and XE-991 (30 μM each), respectively. Treatment with LPS (10 ng/ml) served as a positive control. a . iNOS expression was measured on RNA level by RT-qPCR (H(3) = 11.608, p < 0.009) and on b protein level by immunocytochemistry (H(3) = 17.665, p = 0.001). c Release of NO was measured by Griess assay (μmol/l; H(3) = 15.784, p = 0.001). Characterization of the anti-inflammatory phenotype of activated microglia by expression of CD206, release of insulin-like growth factor 1 (IGF1), and change of phagocytic capacity, after pharmacological block of HCN and KCNQ/Kv7 channels by 30 μM ZD7288 and XE-991, respectively. Treatment with IL4 (25 ng/ml) served as a positive control. d Regulation of CD206 expression on RNA level was measured by RT-qPCR (F (3, 20) = 13.981, p < 0.0001, ω = 0.62). e IGF1 release was measured by ELISA (pg/ml, H(3) = 15.805, p = 0.001). f Zymosan engulfment showed phagocytic activity of microglia (H(3) = 11.653, p < 0.009). Data were blank-corrected and normalized to control. g Representative immunocytochemical stainings for the microglia marker Iba1 (red), co-stained for iNOS (green), and Hoechst as a nuclear counterstain (blue); scale bars = 50 μm

    Article Snippet: Microglia were left unstimulated (control) or were stimulated with 10 ng/ml lipopolysaccharide (LPS derived from E. coli 0111: B4, Sigma Aldrich, St. Louis, USA) to activate microglia towards a pro-inflammatory phenotype, or alternatively stimulated with 50 ng/ml recombinant rat interleukin-4 (IL4; Peprotech, Hamburg, Germany) to polarize microglia to an anti-inflammatory phenotype [ ].

    Techniques: Activation Assay, Expressing, Positive Control, Quantitative RT-PCR, Immunocytochemistry, Griess Assay, Blocking Assay, Enzyme-linked Immunosorbent Assay, Activity Assay, Marker, Staining

    Impact of functional HCN and KCNQ/Kv7 channels on the activation capacity of primary microglia. * p < 0.05; ** p < 0.01; *** p < 0.001. Stimulation of microglia with LPS (10 ng/ml) with simultaneous blockade of the HCN or the KCNQ/Kv7 channel and resulting expression of pro-inflammatory markers. The HCN channel was either blocked pharmacologically with ZD7288 (30 μM) or by transfection of silencer® small interfering (si)RNA targeting HCN2-mRNA (siHCN2-RNA). XE-991 (30 μM) was used to block KCNQ/Kv7. a Inducible nitric oxide (NO) synthase (iNOS) expression was measured on RNA level by RT-qPCR (H(3) = 17.142, p = 0.001) and on b protein level by immunocytochemistry (H(3) = 19.626, p < 0.0001). c NO release was measured by Griess assay (μmol/l; H(3) = 23.102, p < 0.0001). Data were normalized to LPS-only stimulation. Characterization of the anti-inflammatory microglia phenotype by the expression of CD206, release of insulin-like growth factor 1 (IGF1), and measurement of the phagocytic activity, after treatment with IL4 (50 ng/ml) and simultaneous blockade of the HCN and KCNQ/Kv7 channel as described above. d Regulation of CD206 expression was measured on RNA level by RT-qPCR (H(3) = 12.755, p = 0.005). e Release of IGF1 was measured by ELISA (pg/ml; H(3) = 16.611, p = 0.001). f Zymosan engulfment indicated phagocytotic activity of microglia (H(2) = 7.501, p = 0.024). Data were normalized to IL4-only stimulation. g Representative images of the immunocytochemical staining for the microglia marker Iba1 (red), co-stained for iNOS (green), and Hoechst as a nuclear counterstain (blue); scale bars = 50 μm

    Journal: Journal of Neuroinflammation

    Article Title: The impact of hyperpolarization-activated cyclic nucleotide-gated (HCN) and voltage-gated potassium KCNQ/Kv7 channels on primary microglia function

    doi: 10.1186/s12974-020-01779-4

    Figure Lengend Snippet: Impact of functional HCN and KCNQ/Kv7 channels on the activation capacity of primary microglia. * p < 0.05; ** p < 0.01; *** p < 0.001. Stimulation of microglia with LPS (10 ng/ml) with simultaneous blockade of the HCN or the KCNQ/Kv7 channel and resulting expression of pro-inflammatory markers. The HCN channel was either blocked pharmacologically with ZD7288 (30 μM) or by transfection of silencer® small interfering (si)RNA targeting HCN2-mRNA (siHCN2-RNA). XE-991 (30 μM) was used to block KCNQ/Kv7. a Inducible nitric oxide (NO) synthase (iNOS) expression was measured on RNA level by RT-qPCR (H(3) = 17.142, p = 0.001) and on b protein level by immunocytochemistry (H(3) = 19.626, p < 0.0001). c NO release was measured by Griess assay (μmol/l; H(3) = 23.102, p < 0.0001). Data were normalized to LPS-only stimulation. Characterization of the anti-inflammatory microglia phenotype by the expression of CD206, release of insulin-like growth factor 1 (IGF1), and measurement of the phagocytic activity, after treatment with IL4 (50 ng/ml) and simultaneous blockade of the HCN and KCNQ/Kv7 channel as described above. d Regulation of CD206 expression was measured on RNA level by RT-qPCR (H(3) = 12.755, p = 0.005). e Release of IGF1 was measured by ELISA (pg/ml; H(3) = 16.611, p = 0.001). f Zymosan engulfment indicated phagocytotic activity of microglia (H(2) = 7.501, p = 0.024). Data were normalized to IL4-only stimulation. g Representative images of the immunocytochemical staining for the microglia marker Iba1 (red), co-stained for iNOS (green), and Hoechst as a nuclear counterstain (blue); scale bars = 50 μm

    Article Snippet: Microglia were left unstimulated (control) or were stimulated with 10 ng/ml lipopolysaccharide (LPS derived from E. coli 0111: B4, Sigma Aldrich, St. Louis, USA) to activate microglia towards a pro-inflammatory phenotype, or alternatively stimulated with 50 ng/ml recombinant rat interleukin-4 (IL4; Peprotech, Hamburg, Germany) to polarize microglia to an anti-inflammatory phenotype [ ].

    Techniques: Functional Assay, Activation Assay, Expressing, Transfection, Blocking Assay, Quantitative RT-PCR, Immunocytochemistry, Griess Assay, Activity Assay, Enzyme-linked Immunosorbent Assay, Staining, Marker

    Primer Specifications.

    Journal: Brain, behavior, and immunity

    Article Title: Immunization with Mycobacterium vaccae induces an anti-inflammatory milieu in the CNS: attenuation of stress-induced microglial priming, alarmins and anxiety-like behavior

    doi: 10.1016/j.bbi.2018.05.020

    Figure Lengend Snippet: Primer Specifications.

    Article Snippet: Recombinant rat IL4 (rIL4) treatment Vehicle (sterile 1x PBS + 0.1% BSA) or rIL4 (100 ng dissolved in vehicle; R & D Systems, cat. no. 504-RL) was injected intra-cisterna magna (i.c.m.

    Techniques: Sequencing, Activation Assay

    Animals received injections of either vehicle or rIL4 (100 ng, i.c.m.). IL4-sensitive target genes were measured in hippocampus at 2 h (N = 6–8 per group) or 24 h post-injection (N = 4 per group). Data are presented as the mean + s.e.m. Significant M. vaccae effects compared to vehicle at each timepoint post-injection, * p < 0.05, ** p < 0.01.

    Journal: Brain, behavior, and immunity

    Article Title: Immunization with Mycobacterium vaccae induces an anti-inflammatory milieu in the CNS: attenuation of stress-induced microglial priming, alarmins and anxiety-like behavior

    doi: 10.1016/j.bbi.2018.05.020

    Figure Lengend Snippet: Animals received injections of either vehicle or rIL4 (100 ng, i.c.m.). IL4-sensitive target genes were measured in hippocampus at 2 h (N = 6–8 per group) or 24 h post-injection (N = 4 per group). Data are presented as the mean + s.e.m. Significant M. vaccae effects compared to vehicle at each timepoint post-injection, * p < 0.05, ** p < 0.01.

    Article Snippet: Recombinant rat IL4 (rIL4) treatment Vehicle (sterile 1x PBS + 0.1% BSA) or rIL4 (100 ng dissolved in vehicle; R & D Systems, cat. no. 504-RL) was injected intra-cisterna magna (i.c.m.

    Techniques: Injection

    Animals received 3 injections of either vehicle or M. vaccae (0.1 mg, s.c.). Eight d after the third injection, (A) IL4 mRNA expression and (B) IL4 protein levels were measured in dorsal, intermediate, and ventral hippocampus. Data are presented as the mean + s.e.m. N = 8 animals per experimental group. Significant main effect of M. vaccae compared to vehicle, * p < 0.05.

    Journal: Brain, behavior, and immunity

    Article Title: Immunization with Mycobacterium vaccae induces an anti-inflammatory milieu in the CNS: attenuation of stress-induced microglial priming, alarmins and anxiety-like behavior

    doi: 10.1016/j.bbi.2018.05.020

    Figure Lengend Snippet: Animals received 3 injections of either vehicle or M. vaccae (0.1 mg, s.c.). Eight d after the third injection, (A) IL4 mRNA expression and (B) IL4 protein levels were measured in dorsal, intermediate, and ventral hippocampus. Data are presented as the mean + s.e.m. N = 8 animals per experimental group. Significant main effect of M. vaccae compared to vehicle, * p < 0.05.

    Article Snippet: Recombinant rat IL4 (rIL4) treatment Vehicle (sterile 1x PBS + 0.1% BSA) or rIL4 (100 ng dissolved in vehicle; R & D Systems, cat. no. 504-RL) was injected intra-cisterna magna (i.c.m.

    Techniques: Injection, Expressing

    Schematic Illustration of Preparation of IL4-Loaded NHG-MSa

    Journal: ACS applied materials & interfaces

    Article Title: Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus

    doi: 10.1021/acsami.7b18458

    Figure Lengend Snippet: Schematic Illustration of Preparation of IL4-Loaded NHG-MSa

    Article Snippet: Recombinant rat IL4 (R&D system) was reconstituted at a concentration of 4 μ g/mL in sterile Dulbecco’s phosphate-buffered saline (DPBS) (Gibco) containing 0.1% bovine serum albumin (BSA, Sigma-Aldrich).

    Techniques:

    Characterizations of IL4-loaded NHG-MS and NG-MS and their release profiles. (A–C) Stacked confocal images of IL4-loaded NHG-MS. (D–F) Cross-sectional confocal images at a higher magnification, showing that IL4 (red) was evenly distributed in the NHG-MS (green). (G) Loading efficiency of IL4 in NHG-MS and NG-MS. (H) Release profiles of IL4 from NHG-MS and NG-MS. (I) Total amount of IL4 (released and unreleased) from the NHG-MS and NG-MS detected via an ELISA (**P < 0.01).

    Journal: ACS applied materials & interfaces

    Article Title: Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus

    doi: 10.1021/acsami.7b18458

    Figure Lengend Snippet: Characterizations of IL4-loaded NHG-MS and NG-MS and their release profiles. (A–C) Stacked confocal images of IL4-loaded NHG-MS. (D–F) Cross-sectional confocal images at a higher magnification, showing that IL4 (red) was evenly distributed in the NHG-MS (green). (G) Loading efficiency of IL4 in NHG-MS and NG-MS. (H) Release profiles of IL4 from NHG-MS and NG-MS. (I) Total amount of IL4 (released and unreleased) from the NHG-MS and NG-MS detected via an ELISA (**P < 0.01).

    Article Snippet: Recombinant rat IL4 (R&D system) was reconstituted at a concentration of 4 μ g/mL in sterile Dulbecco’s phosphate-buffered saline (DPBS) (Gibco) containing 0.1% bovine serum albumin (BSA, Sigma-Aldrich).

    Techniques: Enzyme-linked Immunosorbent Assay

    In vitro bioactivity assay of the IL4 released from NHG-MS. Bone marrow-derived macrophages (BMDMs) stimulated by LPS and IFN-γ for 24 h were polarized into M1 proinflammatory macrophages and then exposed to IL4 released from NHG-MS at 1 and 14 days for 24 h. The LPS + IFN-γ-only and the LPS + IFN-γ + IL4 groups were used as negative and positive controls, respectively. (A, B) Immunofluorescence images and quantitative analysis of CD206+ (green, an M2 macrophage marker) and CD68+ (red, pan-macrophage marker) BMDMs. Cells treated with the LPS + IFN-γ-only group exhibited a rounded morphology, and CD206+ cells were barely detected in this negative control group, indicating the proinflammatory M1 phenotype. By contrast, addition of IL4 released from NHG-MS at 1 and 14 days switched the cells into typical elongated spindle shapes, and approximately 70% BMDMs were CD206+CD68+ M2 phenotype, which was similar to the IL4 positive control group. (C, D) Quantitative analysis of proinflammatory cytokines in the supernatant showed the significant reduction of both TNF-α and IL6 in three groups with additional IL4 treatment (**P < 0.01).

    Journal: ACS applied materials & interfaces

    Article Title: Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus

    doi: 10.1021/acsami.7b18458

    Figure Lengend Snippet: In vitro bioactivity assay of the IL4 released from NHG-MS. Bone marrow-derived macrophages (BMDMs) stimulated by LPS and IFN-γ for 24 h were polarized into M1 proinflammatory macrophages and then exposed to IL4 released from NHG-MS at 1 and 14 days for 24 h. The LPS + IFN-γ-only and the LPS + IFN-γ + IL4 groups were used as negative and positive controls, respectively. (A, B) Immunofluorescence images and quantitative analysis of CD206+ (green, an M2 macrophage marker) and CD68+ (red, pan-macrophage marker) BMDMs. Cells treated with the LPS + IFN-γ-only group exhibited a rounded morphology, and CD206+ cells were barely detected in this negative control group, indicating the proinflammatory M1 phenotype. By contrast, addition of IL4 released from NHG-MS at 1 and 14 days switched the cells into typical elongated spindle shapes, and approximately 70% BMDMs were CD206+CD68+ M2 phenotype, which was similar to the IL4 positive control group. (C, D) Quantitative analysis of proinflammatory cytokines in the supernatant showed the significant reduction of both TNF-α and IL6 in three groups with additional IL4 treatment (**P < 0.01).

    Article Snippet: Recombinant rat IL4 (R&D system) was reconstituted at a concentration of 4 μ g/mL in sterile Dulbecco’s phosphate-buffered saline (DPBS) (Gibco) containing 0.1% bovine serum albumin (BSA, Sigma-Aldrich).

    Techniques: In Vitro, Derivative Assay, Immunofluorescence, Marker, Negative Control, Positive Control

    Macrophage phenotype in the defect area 7 days after surgical operation: iNOS (green, an M1 macrophage marker); CD206 (green, an M2 macrophage marker); and CD68 (red, pan-macrophage marker). (A) Immunofluorescence images showed that iNOS was extensively expressed in the DM and DM + NHG-MS groups. In comparison, the expression of iNOS in the IL4-loaded NHG-MS DM group was much less, which is similar to the normal control group, indicating fewer M1 macrophages in the normal control and IL4-loaded NHG-MS DM groups than the other two DM groups. (B) Immunofluorescence images showed that the expression of CD206 in the IL4-loaded NHG-MS DM group was similar to that in the normal control group and much higher than that in the other two DM groups. (C–F) Quantitative analysis showed that the expression of CD68 was significantly higher in the three DM groups than that in the normal control group (C), indicating that more macrophages infiltrated into the defect site of diabetic rats. Fewer M1 macrophages and more M2 macrophages in both the normal control and IL4-loaded NHG-MS DM groups (D, E) resulted in significantly higher M2/M1 ratios than in the other two DM groups (F) (**P < 0.01).

    Journal: ACS applied materials & interfaces

    Article Title: Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus

    doi: 10.1021/acsami.7b18458

    Figure Lengend Snippet: Macrophage phenotype in the defect area 7 days after surgical operation: iNOS (green, an M1 macrophage marker); CD206 (green, an M2 macrophage marker); and CD68 (red, pan-macrophage marker). (A) Immunofluorescence images showed that iNOS was extensively expressed in the DM and DM + NHG-MS groups. In comparison, the expression of iNOS in the IL4-loaded NHG-MS DM group was much less, which is similar to the normal control group, indicating fewer M1 macrophages in the normal control and IL4-loaded NHG-MS DM groups than the other two DM groups. (B) Immunofluorescence images showed that the expression of CD206 in the IL4-loaded NHG-MS DM group was similar to that in the normal control group and much higher than that in the other two DM groups. (C–F) Quantitative analysis showed that the expression of CD68 was significantly higher in the three DM groups than that in the normal control group (C), indicating that more macrophages infiltrated into the defect site of diabetic rats. Fewer M1 macrophages and more M2 macrophages in both the normal control and IL4-loaded NHG-MS DM groups (D, E) resulted in significantly higher M2/M1 ratios than in the other two DM groups (F) (**P < 0.01).

    Article Snippet: Recombinant rat IL4 (R&D system) was reconstituted at a concentration of 4 μ g/mL in sterile Dulbecco’s phosphate-buffered saline (DPBS) (Gibco) containing 0.1% bovine serum albumin (BSA, Sigma-Aldrich).

    Techniques: Marker, Immunofluorescence, Comparison, Expressing, Control

    Expression of proinflammatory cytokines TNF-α in the defect area 7 days after the surgical operation. (A–D) Immunohistochemical images showed stronger expression of TNF-α in DM and DM + NHG-MS groups than in normal control and IL4-loaded NHG-MS DM groups. (E, F) Quantitative analysis of TNF-α positive area ratio and mean integral optical density (IOD) (**P < 0.01).

    Journal: ACS applied materials & interfaces

    Article Title: Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus

    doi: 10.1021/acsami.7b18458

    Figure Lengend Snippet: Expression of proinflammatory cytokines TNF-α in the defect area 7 days after the surgical operation. (A–D) Immunohistochemical images showed stronger expression of TNF-α in DM and DM + NHG-MS groups than in normal control and IL4-loaded NHG-MS DM groups. (E, F) Quantitative analysis of TNF-α positive area ratio and mean integral optical density (IOD) (**P < 0.01).

    Article Snippet: Recombinant rat IL4 (R&D system) was reconstituted at a concentration of 4 μ g/mL in sterile Dulbecco’s phosphate-buffered saline (DPBS) (Gibco) containing 0.1% bovine serum albumin (BSA, Sigma-Aldrich).

    Techniques: Expressing, Immunohistochemical staining, Control

    Expression of Osterix and Runx2 in the defect area 14 days after the surgical operation. (A, B) Immunohistochemical images showed significantly more Osterix+ and Runx2+ osteoprogenitor cells in normal control and IL4-loaded NHG-MS DM groups than in the other two DM groups. (C–F) Quantitative analysis of the number of Osterix+ and Runx2+ cells and mean integral optical density (IOD) (*P < 0.05, **P < 0.01).

    Journal: ACS applied materials & interfaces

    Article Title: Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus

    doi: 10.1021/acsami.7b18458

    Figure Lengend Snippet: Expression of Osterix and Runx2 in the defect area 14 days after the surgical operation. (A, B) Immunohistochemical images showed significantly more Osterix+ and Runx2+ osteoprogenitor cells in normal control and IL4-loaded NHG-MS DM groups than in the other two DM groups. (C–F) Quantitative analysis of the number of Osterix+ and Runx2+ cells and mean integral optical density (IOD) (*P < 0.05, **P < 0.01).

    Article Snippet: Recombinant rat IL4 (R&D system) was reconstituted at a concentration of 4 μ g/mL in sterile Dulbecco’s phosphate-buffered saline (DPBS) (Gibco) containing 0.1% bovine serum albumin (BSA, Sigma-Aldrich).

    Techniques: Expressing, Immunohistochemical staining, Control

    ALP staining of the defect area 14 days after the surgical operation. (A–D) Normal control and IL4-loaded NHG-MS DM groups exhibited significantly more extensive and robust ALP expression than in the other two DM groups. (E, F) Quantitative analysis of ALP-positive area ratio and mean integral optical density (IOD) (*P < 0.05, **P < 0.01).

    Journal: ACS applied materials & interfaces

    Article Title: Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus

    doi: 10.1021/acsami.7b18458

    Figure Lengend Snippet: ALP staining of the defect area 14 days after the surgical operation. (A–D) Normal control and IL4-loaded NHG-MS DM groups exhibited significantly more extensive and robust ALP expression than in the other two DM groups. (E, F) Quantitative analysis of ALP-positive area ratio and mean integral optical density (IOD) (*P < 0.05, **P < 0.01).

    Article Snippet: Recombinant rat IL4 (R&D system) was reconstituted at a concentration of 4 μ g/mL in sterile Dulbecco’s phosphate-buffered saline (DPBS) (Gibco) containing 0.1% bovine serum albumin (BSA, Sigma-Aldrich).

    Techniques: Staining, Control, Expressing

    μ-CT three-dimensional reconstruction images of the rat mandible and new regenerated bone 4 weeks after surgery. (A–H) The defect area was entirely occupied by new regenerated bone in both the normal control group and the IL4-loaded NHG-MS DM group. In contrast, only half of the defect region was filled with new bone in the DM and DM + NHG-MS groups. (I) Ratio of bone volume to total volume (BV/TV) in all four groups (**P < 0.01).

    Journal: ACS applied materials & interfaces

    Article Title: Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus

    doi: 10.1021/acsami.7b18458

    Figure Lengend Snippet: μ-CT three-dimensional reconstruction images of the rat mandible and new regenerated bone 4 weeks after surgery. (A–H) The defect area was entirely occupied by new regenerated bone in both the normal control group and the IL4-loaded NHG-MS DM group. In contrast, only half of the defect region was filled with new bone in the DM and DM + NHG-MS groups. (I) Ratio of bone volume to total volume (BV/TV) in all four groups (**P < 0.01).

    Article Snippet: Recombinant rat IL4 (R&D system) was reconstituted at a concentration of 4 μ g/mL in sterile Dulbecco’s phosphate-buffered saline (DPBS) (Gibco) containing 0.1% bovine serum albumin (BSA, Sigma-Aldrich).

    Techniques: Control

    HE staining of the defect area 4 weeks after the surgical operation. (A–D) Newly formed bone filled the entire defect area in the normal control and the IL4-loaded NHG-MS DM group. In comparison, new bone formation was observed on the outer boundary of the defect area in the DM and DM + NHG-MS groups. The yellow arrows indicate newly formed bone, and the blue arrows indicate microspheres.

    Journal: ACS applied materials & interfaces

    Article Title: Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus

    doi: 10.1021/acsami.7b18458

    Figure Lengend Snippet: HE staining of the defect area 4 weeks after the surgical operation. (A–D) Newly formed bone filled the entire defect area in the normal control and the IL4-loaded NHG-MS DM group. In comparison, new bone formation was observed on the outer boundary of the defect area in the DM and DM + NHG-MS groups. The yellow arrows indicate newly formed bone, and the blue arrows indicate microspheres.

    Article Snippet: Recombinant rat IL4 (R&D system) was reconstituted at a concentration of 4 μ g/mL in sterile Dulbecco’s phosphate-buffered saline (DPBS) (Gibco) containing 0.1% bovine serum albumin (BSA, Sigma-Aldrich).

    Techniques: Staining, Control, Comparison