tlr4 inhibitor resatorvid tak 242  (MedChemExpress)

Journal: Cell & Bioscience

Article Title: Gordonibacter-associated regulatory T cell dysfunction and S100A11-mediated neural impairment in Hirschsprung’s disease: a microbiota-immune-neural axis

doi: 10.1186/s13578-026-01562-7

Figure Lengend Snippet: Multi-omics integration identifies molecular dysregulation in HSCR. Concordant dysregulation identified at protein and transcript levels through integrated analysis. A Volcano plot of differentially expressed proteins ( n = 97, fold change > 1.5 or < 0.67, p < 0.05) with S100A11 upregulation prominent. B – F Pathway enrichment demonstrating oxygen transport, hemoglobin complex, calcium signaling alterations, molecular functions, KEGG pathways, and protein-protein interaction networks. G , H Transcriptomic meta-analysis ( GSE96854 n = 30, GSE98502 n = 16) volcano plot and heatmap identifying 287 dysregulated genes (|log₂FC|>1, FDR q < 0.05). I , J Gene expression patterns and GO biological processes showing immune activation, impaired neural development, and calcium signaling disruption. K Five-gene regulatory network (TLR4-MYD88-NFKB1-SOX10-FOXP3) linking microbial recognition, inflammatory activation, and neural-immune interactions. Error bars represent SEM. Statistical significance determined by Benjamini-Hochberg FDR correction (q < 0.05)

Article Snippet: Cells were subjected to serum deprivation for 6 h to establish baseline conditions, then treated with recombinant S100A11 (100 ng/mL; Abcam Cat# ab198977) in combination with either RAGE inhibitor FPS-ZM1 (1 μM; MedChemExpress Cat# HY-19370) or TLR4 inhibitor TAK-242 (5 μM; MedChemExpress Cat# HY-11109).

Techniques: Biomarker Discovery, Gene Expression, Activation Assay, Disruption

Journal: Cell & Bioscience

Article Title: Gordonibacter-associated regulatory T cell dysfunction and S100A11-mediated neural impairment in Hirschsprung’s disease: a microbiota-immune-neural axis

doi: 10.1186/s13578-026-01562-7

Figure Lengend Snippet: S100A11-RAGE-NF-κB signaling impairs neural development and migration. In vitro mechanistic validation demonstrated S100A11-mediated neural cell dysfunction in SH-SY5Y cells. A qRT-PCR showing dose-dependent suppression of SOX10, RET, PHOX2B, CACNA1C following S100A11 treatment (50, 200 ng/mL, 48 h; n = 3 with technical triplicates). B Western blot validation of reduced protein levels. C , D Impaired wound healing (32.4% vs. 78.5%, Cohen’s d = 8.76, p < 0.001) and Transwell migration (67 ± 12 vs. 186 ± 23 cells, Cohen’s d = 6.54, p < 0.001) with partial FPS-ZM1 rescue. E Western blot in tissue cohort ( n = 15) confirming S100A11 elevation, TLR4 activation, SOX10 suppression, and decreased FOXP3. F Temporal NF-κB activation: IκBα phosphorylation (15 min), degradation (30 min), p65 phosphorylation. G FPS-ZM1 blocked 68.4% of p-p65; TAK-242 reduced 53.7%. H Gene expression at 6 h showing inflammatory upregulation (IL-6, TNF-α, VCAM1, ICAM1, CCL2) and neural marker suppression (SOX10, RET, PHOX2B). Mean ± SEM, n = 3–15 with technical triplicates. One-way ANOVA with Tukey post hoc. ** p < 0.01, *** p < 0.001

Article Snippet: Cells were subjected to serum deprivation for 6 h to establish baseline conditions, then treated with recombinant S100A11 (100 ng/mL; Abcam Cat# ab198977) in combination with either RAGE inhibitor FPS-ZM1 (1 μM; MedChemExpress Cat# HY-19370) or TLR4 inhibitor TAK-242 (5 μM; MedChemExpress Cat# HY-11109).

Techniques: Migration, In Vitro, Biomarker Discovery, Quantitative RT-PCR, Western Blot, Activation Assay, Phospho-proteomics, Gene Expression, Marker

Journal: Investigative Ophthalmology & Visual Science

Article Title: Advanced Glycation End-Products Contribute to Delayed Diabetic Corneal Epithelial Wound Healing via the TLR4 Signaling

doi: 10.1167/iovs.67.2.40

Figure Lengend Snippet: TLR4 signaling mediates AGE–BSA-induced inflammation in BMDCs. ( A ) Schematic illustrating TLR4 signaling pathways. ( B ) WB analysis of the phosphorylated p65 and IRF3 in BMDCs after 12 hours of treatment ( n = 4/group). Uncropped immunoblots are shown in A. ( C ) Quantitative real-time PCR analysis of Il12b , Il1β , Cxcl10 , and Ifit1 expression in BMDCs after different treatments ( n = 3/group). ( D ) WB analysis of MyD88 and TRIF in BMDCs after different treatments for 12 hours ( n = 4/group). Uncropped immunoblots are shown in B. ( E ) Quantification of MyD88 and TRIF in the different groups by ImageJ. Con, BMDCs without any treatment; AGE, AGE–BSA-stimulated BMDCs; AGE+TAK-242, BMDCs co-treated with AGE–BSA and TAK-242; AGE+FPS-ZM1, BMDCs stimulated with AGE–BSA in the presence of FPS-ZM1. * P < 0.05, ** P < 0.01, *** P < 0.001.

Article Snippet: To determine the role of TLR4 signaling on diabetic CEWH, the TLR4 signaling inhibitor TAK-242 (6 μL, 0.375 mg/mL; MedChemExpress, Monmouth Junction, NJ, USA) was administrated via subconjunctival injection immediately following abrasion, as previously described.

Techniques: Protein-Protein interactions, Western Blot, Real-time Polymerase Chain Reaction, Expressing

Journal: Investigative Ophthalmology & Visual Science

Article Title: Advanced Glycation End-Products Contribute to Delayed Diabetic Corneal Epithelial Wound Healing via the TLR4 Signaling

doi: 10.1167/iovs.67.2.40

Figure Lengend Snippet: Blocking TLR4 signaling suppresses AGE–BSA-induced inflammation in BMDCs. ( A ) PCA plot showing the expression profiles of the Inhib and AGE groups. ( B ) Volcano plot of DEGs in the Inhib versus AGE groups. ( C ) GSEA showing enriched immune responses in the downregulated DEGs. ( D ) The top enriched BPs in the downregulated DEGs ( n = 3/group). ( E ) Quantitative real-time PCR analysis of the selected inflammatory genes ( Cxcl10 , Ifit1 , Ifnβ1 , Il1β , Il6 , and Il12b ) in BMDCs from the different groups ( n = 6/group). ( F ) The level of IFN-β in supernatant of the different groups as determined by ELISA ( n = 6/group). ( G ) WB analysis of the phosphorylated p65, TBK1, and IRF3 in BMDCs with different treatments ( n = 4/group). Uncropped immunoblots are shown in . ( H ) The expression and location of phospho-IRF3 ( red ) and phospho-p65 ( green ) in BMDCs from the different groups as determined by IF. Nuclei were counterstained with DAPI ( blue ). Scale bars : 30 µm. AGE, BMDCs stimulated with AGE–BSA in the absence of TAK-242; Inhib, BMDCs stimulated with AGE–BSA in the presence of TAK-242. *** P < 0.001, **** P < 0.0001.

Article Snippet: To determine the role of TLR4 signaling on diabetic CEWH, the TLR4 signaling inhibitor TAK-242 (6 μL, 0.375 mg/mL; MedChemExpress, Monmouth Junction, NJ, USA) was administrated via subconjunctival injection immediately following abrasion, as previously described.

Techniques: Blocking Assay, Expressing, Inhibition, Real-time Polymerase Chain Reaction, Enzyme-linked Immunosorbent Assay, Western Blot

Journal: Investigative Ophthalmology & Visual Science

Article Title: Advanced Glycation End-Products Contribute to Delayed Diabetic Corneal Epithelial Wound Healing via the TLR4 Signaling

doi: 10.1167/iovs.67.2.40

Figure Lengend Snippet: Shared inflammatory transcriptome in diabetic corneas and AGE-stimulated BMDCs. ( A ) Venn diagrams show the numbers of common DEGs between AGE-treated BMDCs and diabetic corneal samples. ( B ) Heatmap of representative shared DEGs in AGE-treated BMDCs and diabetic corneal samples. ( C ) The top significantly enriched BPs among shared DEGs. ( D ) Heatmap illustrating the common DEGs in AGE-challenged BMDCs after TAK-242 treatment. DM-Cornea, corneas from T1DM mice; Nor-Cornea, corneas from age-matched mice; BSA, BMDCs exposed to BSA; AGE, BMDCs exposed to AGE–BSA in the absence of TAK-242; inhib, BMDCs exposed to AGE–BSA in the presence of TAK-242.

Article Snippet: To determine the role of TLR4 signaling on diabetic CEWH, the TLR4 signaling inhibitor TAK-242 (6 μL, 0.375 mg/mL; MedChemExpress, Monmouth Junction, NJ, USA) was administrated via subconjunctival injection immediately following abrasion, as previously described.

Techniques: Inhibition

Journal: Investigative Ophthalmology & Visual Science

Article Title: Advanced Glycation End-Products Contribute to Delayed Diabetic Corneal Epithelial Wound Healing via the TLR4 Signaling

doi: 10.1167/iovs.67.2.40

Figure Lengend Snippet: Inhibition of AGE/TLR4 signaling promotes CEWH and nerve regeneration. ( A ) Schematic strategy depicting establishment of the murine T1DM model followed by corneal abrasion and treatment with negative control vehicle or TAK-242. ( B ) Representative slit-lamp images of corneal defects with different treatments at 0, 24, and 48 hours post-injury. ( C ) Quantification of epithelial defect area as in B determined by ImageJ ( n = 6/group). ( D ) Western blot analysis of phosphorylated STAT3 and AKT in corneal tissues at 48 hours post-injury ( n = 4/group). Uncropped immunoblots are shown in B. ( E ) Relative level of phosphorylated STAT3 and AKT in corneal tissues as determined by ImageJ. ( F ) Immunostaining of STAT3 ( green ) and KI67 ( green ) in corneas under different conditions. Nuclei were counterstained with DAPI ( blue ). Scale bars : 40 µm. ( G ) Representative images of regenerated corneal nerve fibers observed by β-tubulin III staining at 7 days post-injury. ( Upper ) Full cornea overview. Scale bar : 400 µm. ( Bottom left ) Central corneas. Scale bar : 200 µm. ( Bottom right ) Peripheral corneas. Scale bar : 200 µm. ( H ) Quantified nerve density in central and peripheral corneas as in G determined by ImageJ ( n = 6/group). Nor, age-matched mice with corneal epithelial abrasion; DM, T1DM mice with corneal epithelial abrasion; DM+TAK-242, T1DM mice with corneal epithelial abrasion following TAK-242 treatment. * P < 0.05, ** P < 0.01, *** P < 0.001; ns, no significance.

Article Snippet: To determine the role of TLR4 signaling on diabetic CEWH, the TLR4 signaling inhibitor TAK-242 (6 μL, 0.375 mg/mL; MedChemExpress, Monmouth Junction, NJ, USA) was administrated via subconjunctival injection immediately following abrasion, as previously described.

Techniques: Inhibition, Negative Control, Western Blot, Immunostaining, Staining

Journal: Investigative Ophthalmology & Visual Science

Article Title: Advanced Glycation End-Products Contribute to Delayed Diabetic Corneal Epithelial Wound Healing via the TLR4 Signaling

doi: 10.1167/iovs.67.2.40

Figure Lengend Snippet: AGE/TLR4 axis drives chronic inflammation contributing to delayed diabetic CEWH. The deposition of AGEs in diabetic corneal tissues activates TLR4 signaling, triggering chronic inflammation that impairs CEWH. Pharmacological targeting of TLR4 signaling accelerates CEWH and nerve regeneration.

Article Snippet: To determine the role of TLR4 signaling on diabetic CEWH, the TLR4 signaling inhibitor TAK-242 (6 μL, 0.375 mg/mL; MedChemExpress, Monmouth Junction, NJ, USA) was administrated via subconjunctival injection immediately following abrasion, as previously described.

Techniques:

Journal: NPJ Parkinson's Disease

Article Title: LRRK2 R1627P mutation amplifies environmental risk factors induced chronic inflammation and α-synuclein aggregation in the gut of rats

doi: 10.1038/s41531-026-01281-3

Figure Lengend Snippet: a Volcano plot comparing DEGs for RNA-seq in LRRK2 R1627P vs WT, LRRK2 −/− vs WT ( p value < 0.05, fold change >1.2), n = 3. b BP categories in GO enrichment analysis and KEGG pathway of DEGs in LRRK2 R1627P vs WT, n = 3. c BP categories in GO enrichment analysis and KEGG pathway of DEGs in LRRK2 −/− vs WT, n = 3. d Western blot analysis for TLR4, MyD88 and NF-κB protein levels in the small intestine of rats, n = 4. One-way ANOVA was used. e TEM images of rats small intestinal LP. Ec enterocytes, LP lamina propria. Scale bars 5 μm, n = 3. One-way ANOVA was used. f Western blot analysis for CD68 and CD163 protein levels in the small intestine of rats, n = 4. One-way ANOVA was used. g Immunofluorescence staining images of CD68 (green) and CD163 (red) (upper panel), IL-6 (green) and iNOS (red) (down panel) positive cells in the small intestinal LP of rats. Nuclei were stained with DAPI (blue). Scale bar 100 μm, n = 4. One-way ANOVA was used. h Flow cytometry scatter plot of small intestianl LP isolated from rats, n = 3. CD11b + CD68 + CD163 - cells represent M1 population and CD11b + CD68 - CD163 + cells represent M2 population. i Statistical analysis of total macrophages, M1 macrophages and M2 macrophages in the small intestianl LP using flow cytometry. One-way ANOVA was used. j Immunofluorescence staining images of CD68 (green) and p S129 -α-Syn (red) positive cells in the small intestinal LP of rats. Nuclei were stained with DAPI (blue). Scale bar 100 μm, n = 4. k Statistical analysis of immunofluorescence staining. One-way ANOVA was used. Data are presented as mean ± SEM, * p < 0.05, ** p < 0.01.

Article Snippet: TAK-242 administration: TLR4 inhibitor TAK-242 was purchased from MedChemExpress (Monmouth Junction, NJ, USA), HY-11109.

Techniques: RNA Sequencing, Western Blot, Immunofluorescence, Staining, Flow Cytometry, Isolation

Journal: NPJ Parkinson's Disease

Article Title: LRRK2 R1627P mutation amplifies environmental risk factors induced chronic inflammation and α-synuclein aggregation in the gut of rats

doi: 10.1038/s41531-026-01281-3

Figure Lengend Snippet: a HE staining images of the small intestine of LPS-treated rats. The green circles in the lower panels highlight the red blood cells in the LP. Scale bar 100 μm, n = 4. b Images of goblet cells stained with AB-PAS in the small intestine of LPS-treated rats. Scale bar 100 μm, n = 4. c Immunohistochemical staining images of Cleaved caspase 3 in the small intestine of LPS-treated rats. Arrows show apoptotic IECs. Scale bar 100 μm, n = 4. d Western blot analysis for ZO-1, E-cadherin, TLR4, MyD88, NF-κB, CD68 and CD163 protein levels in the small intestine of LPS-treated rats, n = 4. e Immunofluorescence staining images and quantification of CD68/IL-6 (green) and CD163/iNOS/p S129 -α-Syn (red) positive cells in the small intestinal LP of LPS-treated rats. Nuclei were stained with DAPI (blue). Scale bar 100 μm, n = 4. One-way ANOVA was used. Data are presented as mean ± SEM, * p < 0.05, ** p < 0.01.

Article Snippet: TAK-242 administration: TLR4 inhibitor TAK-242 was purchased from MedChemExpress (Monmouth Junction, NJ, USA), HY-11109.

Techniques: Staining, Immunohistochemical staining, Western Blot, Immunofluorescence

Journal: NPJ Parkinson's Disease

Article Title: LRRK2 R1627P mutation amplifies environmental risk factors induced chronic inflammation and α-synuclein aggregation in the gut of rats

doi: 10.1038/s41531-026-01281-3

Figure Lengend Snippet: a The representative small intestine images in rats treated with saline (control) or TLR4 inhibitor (TAK-242). Scale bar 5 cm, n = 8. b HE staining images of small intestine in rats treated with saline (control) or TLR4 inhibitor (TAK-242). Scale bar 100 μm, n = 4. c Measurement of small intestine length ( n = 8), villus height and crypt depth ( n = 4) in rats treated with saline (control) or TLR4 inhibitor (TAK-242). Two-way ANOVA was used; interaction p < 0.0001. d Immunohistochemical staining images of Ki67 in the small intestine, and the quantification of Ki67 positive cells in the crypts (determined based on the number of brown-stained cell nuclei in the crypts). Scale bar 100 μm, n = 4. Two-way ANOVA was used; interaction p < 0.05. e Images and quantification of goblet cells stained with AB-PAS in the small intestine. Scale bar 100 μm, n = 4. Two-way ANOVA was used; interaction p < 0.01. f Images and quantification of immunohistochemical staining for lysozyme in the crypt. Scale bar 100 μm, n = 4. Two-way ANOVA was used; interaction p < 0.01. g Western blot analysis for MUC2, Villin, ZO-1 and E-cadherin protein levels in the small intestine of WT, LRRK2 R1627P and LRRK2 −/− rats treated with saline (control) or TLR4 inhibitor (TAK-242), n = 4. One-way ANOVA was used. Data are presented as mean ± SEM, * p < 0.05, ** p < 0.01.

Article Snippet: TAK-242 administration: TLR4 inhibitor TAK-242 was purchased from MedChemExpress (Monmouth Junction, NJ, USA), HY-11109.

Techniques: Saline, Control, Staining, Immunohistochemical staining, Western Blot

Journal: NPJ Parkinson's Disease

Article Title: LRRK2 R1627P mutation amplifies environmental risk factors induced chronic inflammation and α-synuclein aggregation in the gut of rats

doi: 10.1038/s41531-026-01281-3

Figure Lengend Snippet: a , b Western blot analysis for TLR4, MyD88, NF-κB, CD68 and CD163 protein levels in the small intestine of WT, LRRK2 R1627P and LRRK2 −/− rats treated with saline (control) or TLR4 inhibitor (TAK-242), n = 4. One-way ANOVA was used. c Immunofluorescence staining images and quantification of CD68/IL-6 (green) and CD163/iNOS/p S129 -α-Syn (red) positive cells in the small intestinal LP of rats treated with saline (control) or TLR4 inhibitor (TAK-242). Nuclei were stained with DAPI (blue). Scale bar 100 μm, n = 4. Two-way ANOVA was used; for CD68/IL-6/iNOS analysis interaction p < 0.01; for CD163 analysis interaction p > 0.05; for p S129 -α-Syn analysis interaction p < 0.001. d GO enrichment analysis for DEGs in ConRP vs ConWT, TAKRP vs ConRP, TAKRP vs ConWT, n = 3. e Heatmap of DEGs from ConWT, ConRP and TAKRP group, n = 3. Data are presented as mean ± SEM, * p < 0.05, ** p < 0.01.

Article Snippet: TAK-242 administration: TLR4 inhibitor TAK-242 was purchased from MedChemExpress (Monmouth Junction, NJ, USA), HY-11109.

Techniques: Western Blot, Saline, Control, Immunofluorescence, Staining

Journal: NPJ Parkinson's Disease

Article Title: LRRK2 R1627P mutation amplifies environmental risk factors induced chronic inflammation and α-synuclein aggregation in the gut of rats

doi: 10.1038/s41531-026-01281-3

Figure Lengend Snippet: LRRK2 R1627P mutation significantly reduced intestianl endogenous total LRRK2, pT73-Rab10 protein level and the number of Paneth cells. Compared with age-macthed WT rats, LRRK2 R1627P rats showed shorter small intestine length, villus height, and crypt depth (from 8 months old); a significant decrease in the number of goblet cells, expression of barrier proteins, and microbial community diversity (from 16 months old); and a marked increase in the TLR4/MyD88/NF-κB signaling pathway, the number of M1 macrophages, the expression of p S129 -α-Syn, and the abundance of Lactobacillus (from 16 months old). Long-term administration of the TLR4 inhibitor TAK-242 effectively ameliorated the imbalance in intestinal homeostasis of LRRK2 R1627P rats.

Article Snippet: TAK-242 administration: TLR4 inhibitor TAK-242 was purchased from MedChemExpress (Monmouth Junction, NJ, USA), HY-11109.

Techniques: Mutagenesis, Expressing

Journal: International Journal of Molecular Medicine

Article Title: Targeting of CIRP attenuates osteoarthritis progression via suppressing TLR4/NF-κB/NLRP3 signaling axis

doi: 10.3892/ijmm.2025.5674

Figure Lengend Snippet: Dependence of CIRP-induced chondrocyte damage on TLR4/NF-κB signaling. (A) Cytotoxicity of BAY 11-7082 and TAK-242 on chondrocytes at various concentration for 48 h, assessed using a CCK-8 assay. (B and C) Western blotting showing the protein expression of IκBα in chondrocytes and p65 in the nucleus of chondrocytes following treatment with the two inhibitors. (D and E) Western blotting showing the protein expression NLRP3, cleaved-caspase-1, ASC and IL-1β following treatment with the two inhibitors. (F and G) Western blotting showing the expression of extracellular matrix proteins in chondrocytes following treatment with the two inhibitors. n=3, * P<0.05, ** P<0.01, *** P<0.001. CIRP, cold-inducible RNA-binding protein; TLR4, Toll-like receptor 4; NLRP3, NLR family pyrin domain containing 3; Cle, cleaved.

Article Snippet: TLR4 inhibitor TAK-242 was purchased from Shanghai Xianding Biotechnology Co., Ltd. Primary antibodies directed against inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), MMP1, MMP3, MMP13, Lamin B1, CD63, CD9, 130 kDa cis-Golgi matrix protein 1 (GM130) and GAPDH were purchased from Proteintech Group, Inc., ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) was purchased from ABclonal.

Techniques: Concentration Assay, CCK-8 Assay, Western Blot, Expressing, RNA Binding Assay

Journal: International Journal of Molecular Medicine

Article Title: Targeting of CIRP attenuates osteoarthritis progression via suppressing TLR4/NF-κB/NLRP3 signaling axis

doi: 10.3892/ijmm.2025.5674

Figure Lengend Snippet: Schematic illustration of targeting of CIRP attenuates osteoarthritis progression and the underlying mechanism. CIRP can be secreted in the form of exosomes and acts as a pro-inflammatory factor that activates the TLR4/NF-κB/NLRP3 signaling pathway, promoting the inflammatory response, ECM degradation and the progression of OA. Additionally, CIRP is identified as a target of miR-145, which inhibits its expression in OA. CIRP, cold-inducible RNA-binding protein; TLR4, Toll-like receptor 4; NLRP3, NLR family pyrin domain containing 3; OA, osteoarthritis; ECM, extracellular matrix; miR, microRNA; iNOS, inducible nitric oxide synthase; COX-2, cyclooxygenase-2; MMPs, matrix metalloproteinases.

Article Snippet: TLR4 inhibitor TAK-242 was purchased from Shanghai Xianding Biotechnology Co., Ltd. Primary antibodies directed against inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), MMP1, MMP3, MMP13, Lamin B1, CD63, CD9, 130 kDa cis-Golgi matrix protein 1 (GM130) and GAPDH were purchased from Proteintech Group, Inc., ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) was purchased from ABclonal.

Techniques: Expressing, RNA Binding Assay