Journal: Physiological Reports

Article Title: CXCL10 is a novel anti‐angiogenic factor downstream of p53 in cardiomyocytes

doi: 10.14814/phy2.15304

Figure Lengend Snippet: p53 induced CXCL10 expression in cardiomyocytes. DNA microarray was performed using p53‐overexpressing NRCMs. (a) Scatter plot shows the genes colored blue with >2‐fold upregulate in p53‐overexpressing NRCMs compared with β‐gal. (b) Heat map shows genes colored red with >2‐fold change and green with <0.5‐fold change between β‐gal and p53. (c) Gene ontology analysis. (d, e) The expression of (d) CXCL10 and (e) p21 transcripts was measured by qPCR ( n = 4). Experiments were performed three times with similar results. (f) The protein expression of CXCL10 in culture media of p53‐overexpressing NRCMs was measured by ELISA ( n = 3). * p < 0.05, ** p < 0.01. by Student's t ‐test.

Article Snippet: CXCL10 protein level in conditioned media, secreted from cardiomyocytes, was assessed by Rat IP‐10/CXCL10 ELISA Kit (Elabscience, #E‐EL‐R0546) according to the manufacturer's protocol.

Techniques: Expressing, Microarray, Enzyme-linked Immunosorbent Assay

Journal: Physiological Reports

Article Title: CXCL10 is a novel anti‐angiogenic factor downstream of p53 in cardiomyocytes

doi: 10.14814/phy2.15304

Figure Lengend Snippet: Doxorubicin induced the expression of CXCL10 in cardiomyocytes through p53 in cardiomyocytes. (a–h) NRCMs were stimulated with Doxo for indicated concentration and time. (i–l) NRCMs were transfected with siRNA for p53 (sip53) or control (siCon) for 48 h, followed by stimulation with Doxo for 24 h. The expression of p53 (a, e, i) and CXCL10 (b, f, j) mRNA was measured by qPCR. ( n = 3). (c, g, k) The expression of p53 protein was analyzed by immunoblotting. Representative data are shown. (d, h, l) The band intensities of p53 were measured ( n = 3). Experiments were performed three times with similar results. (a–h). *p < 0.05, **p < 0.01 by one‐way ANOVA followed by Dunnett test. (i–l) * p < 0.05, ** p < 0.01 by one‐way ANOVA followed by Tukey–Kramer test.

Article Snippet: CXCL10 protein level in conditioned media, secreted from cardiomyocytes, was assessed by Rat IP‐10/CXCL10 ELISA Kit (Elabscience, #E‐EL‐R0546) according to the manufacturer's protocol.

Techniques: Expressing, Concentration Assay, Transfection, Control, Western Blot

Journal: Physiological Reports

Article Title: CXCL10 is a novel anti‐angiogenic factor downstream of p53 in cardiomyocytes

doi: 10.14814/phy2.15304

Figure Lengend Snippet: Hypoxia synergistically elevated the expression of CXCL10. p53‐overexpresisng NRCMs were treated with CoCl2 for 24 h. (a) The expression of p53 and GAPDH protein was analyzed by immunoblotting. Representative data were shown. The expression of (b) VEGF and (c) CXCL10 transcripts was measured by qPCR ( n = 4). Experiments were performed three times with similar results. * p < 0.05, ** p < 0.01 by one‐way ANOVA followed by Tukey–Kramer test.

Article Snippet: CXCL10 protein level in conditioned media, secreted from cardiomyocytes, was assessed by Rat IP‐10/CXCL10 ELISA Kit (Elabscience, #E‐EL‐R0546) according to the manufacturer's protocol.

Techniques: Expressing, Western Blot

Journal: Physiological Reports

Article Title: CXCL10 is a novel anti‐angiogenic factor downstream of p53 in cardiomyocytes

doi: 10.14814/phy2.15304

Figure Lengend Snippet: p53‐induced CXCL10, secreted from cardiomyocytes, inhibited the tube formation of endothelial cells. Culture media were collected from p53‐ or β‐gal‐overexpressing NRCMs. RAOECs were cultured with the conditioned media in the presence of AMG487, an inhibitor of CXCR3. Angiogenesis assay was performed. (a) Representative images were shown. (b) The number of tube formation was measured ( n = 6). * p < 0.05, ** p < 0.01 by one‐way ANOVA followed by Tukey–Kramer test.

Article Snippet: CXCL10 protein level in conditioned media, secreted from cardiomyocytes, was assessed by Rat IP‐10/CXCL10 ELISA Kit (Elabscience, #E‐EL‐R0546) according to the manufacturer's protocol.

Techniques: Cell Culture, Angiogenesis Assay

Journal: Journal of nanobiotechnology

Article Title: Unveiling the improved targeting migration of mesenchymal stem cells with CXC chemokine receptor 3-modification using intravital NIR-II photoacoustic imaging.

doi: 10.1186/s12951-022-01513-7

Figure Lengend Snippet: Fig. 4 Upregulation of Cxcl10 in inflamed ears of CHS mice. a Representative photographs of mouse ears challenged with vehicle (Control) or DNFB (Inflamed). Photos were taken 24 h after challenging. b Thickness of mice ears challenged with vehicle (Control) or DNFB (Inflamed) before (Pre), 24 h and 72 h after challenging (n = 3–4 per group). c mRNA expression of Cxcl10 transcript in mouse ears challenged with vehicle (Control) or DNFB (Inflamed) (n = 3 per group). ***P < 0.001; ns, no significance; error bars, SEM

Article Snippet: Rabbit polyclonal antibody against Cxcr3 (NB100-56404), recombinant Cxcl10 protein (466- CR) were purchased from R&D systems (Minneapolis, MN, USA).

Techniques: Control, Expressing

Journal: Journal of nanobiotechnology

Article Title: Unveiling the improved targeting migration of mesenchymal stem cells with CXC chemokine receptor 3-modification using intravital NIR-II photoacoustic imaging.

doi: 10.1186/s12951-022-01513-7

Figure Lengend Snippet: Fig. 5 Overexpression of Cxcr3 in MSCs. a Representative bright field (BF) and green fluorescence images of MSCeGFP and MSCCxcr3. MSCs were transduced with lentivirus to express eGFP alone (MSCeGFP) or in combination with Cxcr3 (MSCCxcr3). b Analysis of Cxcr3 mRNA expression in MSCeGFP and MSCCxcr3.c Western blot of Cxcr3 in total cell lysates of MSCeGFP and MSCCxcr3. CypB, cyclophilin B, used as housekeeping gene. d Cxcr3 overexpression promoted the in vitro migration of MSCs toward Cxcl10. Representative images and quantification analysis of transwell migration assay were shown. e Quantification analysis of transwell migration assay of MSCCxcr3 after incubating with vehicle (PBS) or TAT-CPNPs (NPs). Scale bars, 100 µm. *P < 0.05, ***P < 0.001; error bars, SEM

Article Snippet: Rabbit polyclonal antibody against Cxcr3 (NB100-56404), recombinant Cxcl10 protein (466- CR) were purchased from R&D systems (Minneapolis, MN, USA).

Techniques: Over Expression, Fluorescence, Transduction, Expressing, Western Blot, In Vitro, Migration, Transwell Migration Assay

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: DNA sequences of the primers used for traditional and real time RT-PCR

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Amplification

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: Partial list of genes that were up or down-regulated by LCN2 as determined by DNA microarray analysis of astrocytes Genes whose expression was increased or decreased greater than 1.5- or 3.5-fold, respectively, by LCN2 were listed.

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Microarray, Expressing, Sequencing, Ubiquitin Proteomics, Binding Assay, Variant Assay

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: Induction of chemokine gene expression by LCN2 in astrocytes, microglia, endothelial cells, and neuron cells. Astrocytes (A and E), microglia (B and E), bEnd.3 endothelial cells (C), and neuron cells (D) were treated with the recombinant LCN2 protein (10 μg/ml) for 8 h, and the total RNA was isolated for traditional RT-PCR or real time PCR. The cells were also treated for 8 h with LPS (100 ng/ml), TNF-α (10 ng/ml), or LPS (100 ng/ml) plus IFN-γ (50 units/ml) for comparison purposes. The mRNA levels of chemokines (CCL4, CCL20, CXCL2, and CXCL10) and other inflammatory genes (IL-6, COX-2, iNOS, and PIAS3) were determined by traditional RT-PCR (A–D) or real time PCR (E). β-Actin or GAPDH was used as an internal control. The results are one representative of more than three independent experiments (A–D) or means ± S.D. (n = 3) (E).

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Gene Expression, Recombinant, Isolation, Reverse Transcription Polymerase Chain Reaction, Real-time Polymerase Chain Reaction, Comparison, Control

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: An increase of CXCL10 expression by LCN2 in astrocytes. Astrocytes were incubated with the recombinant LCN2 protein (10 μg/ml) or LPS (100 ng/ml) plus IFN-γ (50 units/ml) for 24 h. The amounts of CXCL10 protein in the culture media were measured by specific ELISA (A). The results are means ± S.D. (n = 3). *, p < 0.05 compared with the untreated control. The stable overexpression or knockdown of lcn2 expression was achieved by transfection with sense or antisense lcn2 cDNA in C6 rat glioma cells. The increased or decreased lcn2 expression in the stable transfectants (S3, lcn2 sense transfectant; AS7, lcn2 antisense transfectant) compared with cells transfected with an empty vector (V2) was confirmed by RT-PCR (B). Changes in the CXCL10 mRNA levels in the stable transfectants were also assessed by RT-PCR (C). β-Actin was used as an internal control. The results are one representative of more than three independent experiments.

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Expressing, Incubation, Recombinant, Enzyme-linked Immunosorbent Assay, Control, Over Expression, Knockdown, Transfection, Plasmid Preparation, Reverse Transcription Polymerase Chain Reaction

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: Astrocyte-derived CXCL10 promoted the migration of astrocytes. Astrocytes (1 × 104 cells/upper well) were exposed to LCN2 (10 μg/ml)-stimulated ACM or the recombinant CXCL10 protein (10 ng/ml) in the presence or absence of CXCL10 neutralizing antibody (CXCL10 Ab; 10 ng/ml) as indicated. ACM-None, untreated ACM; ACM-LCN2, LCN2-treated ACM (see “Experimental Procedures” for the preparation of ACM). After treatment for the indicated time periods, either wound healing assay (A) or the Boyden chamber assay (B) was performed to evaluate cell migration. A representative microscopic image for each condition was shown (magnification, ×100) (upper). The quantification of cell migration was done by either measuring the degree of wound closure (wound healing assay) or enumerating the migrated cells (Boyden chamber assay) as described under “Experimental Procedures” (lower). The results are means ± S.D. (n = 3). *, p < 0.05 compared with ACM-None at the same time point; **, p < 0.05 compared with ACM-LCN2 at the same time point; #, p < 0.05 compared with the untreated control (None) at the same time point. For the checkerboard analysis, migration of astrocytes (2 × 104 cells/upper well) in response to the indicated concentrations of ACM-LCN2 (C) and the recombinant CXCL10 protein (D) placed in upper and/or lower well was determined using the Boyden chamber assay. The quantification of cell migration was done by enumerating the migrated cells after 48 h as described under “Experimental Procedures.” The results are the means ± S.D. (n = 3). *, p < 0.05 between the treatments indicated.

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Derivative Assay, Migration, Recombinant, Wound Healing Assay, Boyden Chamber Assay, Control

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: Checkerboard analysis for promigratory effects of recombinant CXCL10 protein in astrocytes The recombinant CXCL10 protein was added to the upper and/or lower wells of the Boyden chambers for the checkerboard analysis. After cells were incubated at 37 °C under 5% CO 2 for 48 h, cell migration was assessed as described under “Experimental Procedures.” NT, not tested.

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Recombinant, Incubation, Migration

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: The effects of LCN2 protein expressed in mammalian cells (mLCN2) on the chemokine gene expression and cell migration in astrocytes. Astrocytes were treated with the NSO murine melanoma cell-derived mouse LCN2 protein (10 μg/ml; mLCN2) for 8 h, and the total RNA was isolated for traditional RT-PCR. The cells were also treated for 8 h with LPS (100 ng/ml) plus IFN-γ (50 units/ml) for comparison purposes. The mRNA levels of CXCL10 and PIAS3 were determined by traditional RT-PCR (A). β-Actin was used as an internal control. The results are one representative of more than three independent experiments. Astrocytes (1 × 104 cells/upper well) were exposed to the melanoma cell-expressed LCN2 protein (10 μg/ml; mLCN2)-stimulated astrocyte-conditioned media (ACM-mLCN2). Astrocytes placed in the Boyden chambers were then incubated at 37 °C for 24–72 h to evaluate cell migration (B). A representative microscopic image for each condition was shown (magnification, ×100) (upper). ACM-None, untreated ACM; ACM-mLCN2, mLCN2-treated ACM. The quantification of cell migration was done by enumerating the migrated cells as described under “Experimental Procedures” (lower). The results are the means ± S.D. (n = 3). *, p < 0.05 compared with ACM-None at the same time point.

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Gene Expression, Migration, Derivative Assay, Isolation, Reverse Transcription Polymerase Chain Reaction, Comparison, Control, Incubation

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: Astrocyte-derived CXCL10 promoted the migration of microglia and neuron cells. Microglia (1 × 104 cells/upper well) (A) or neuron cells (1 × 104 cells/upper well) (B) were exposed to LCN2 (10 μg/ml)-stimulated ACM or the recombinant CXCL10 protein (10 ng/ml) in the presence or absence of CXCL10 neutralizing antibody (10 ng/ml) as indicated. Microglia or neuron cells placed in the Boyden chambers were incubated at 37 °C for 12–48 or 18–48 h, respectively, to evaluate cell migration. The GST protein (10 μg/ml) was used as a control for the recombinant LCN2 protein. A representative microscopic image for each condition is shown (magnification, ×100) (upper). ACM-None, untreated ACM; ACM-LCN2, LCN2-treated ACM. The quantification of cell migration was done by enumerating the migrated cells as described under “Experimental Procedures” (lower). The results are the means ± S.D. (n = 3). *, p < 0.05 compared with ACM-None at the same time point; **, p < 0.05 compared with ACM-LCN2 at the same time point; #, p < 0.05 compared with the untreated control (None) at the same time point.

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Derivative Assay, Migration, Recombinant, Incubation, Control

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: JAK2/STAT3 and IKK/NF-κB mediated LCN2 up-regulation of CXCL10 and GFAP expression in astrocytes. Astrocytes were pretreated with the recombinant LCN2 protein (10 μg/ml) for 24 h prior to the treatment with phorbol 12-myristate 13-acetate (100 μg/ml), ATP (3 mm), or IFN-γ (50 units/ml) for 30 min. Astrocytes were also exposed to phorbol 12-myristate 13-acetate (PMA), ATP, or IFN-γ for 30 min without LCN2 pretreatment (A). Alternatively, astrocytes were treated with LCN2 for 0.5–24 h for the time kinetics analysis (B). The levels of phosphorylated STAT3 (pSTAT3 at Ser727 or Tyr705) or total STAT3 protein were then evaluated by Western blot analysis. The results are one representative of more than three independent experiments. Alternatively, astrocytes were pretreated with AG490 (JAK2/STAT3-specific inhibitor, 50 μm) or piceatannol (JAK1/STAT1-specific inhibitor, 50 μm) for 30 min prior to the treatment with the recombinant LCN2 protein (10 μg/ml) or LPS (100 ng/ml) plus IFN-γ (50 units/ml) for 24 h. The secreted CXCL10 protein was measured by specific ELISA (C). The results are the means ± S.D. (n = 3). *, p < 0.001 compared with the treatment without inhibitors. Astrocytes were pretreated with AG490 for 30 min prior to the treatment with the recombinant LCN2 protein (10 μg/ml) for 24 h. The expression of GFAP protein levels was assessed by Western blot analysis, respectively (D). After astrocytes were treated with the recombinant LCN2 protein (10 μg/ml) or LPS (100 ng/ml) plus IFN-γ (50 units/ml) for 1 h, an EMSA analysis of the nuclear extracts was conducted by using a 32P-labeled NF-κB oligonucleotide probe (E). Binding specificity was determined by the supershift assay using antibody against p65 (p65 Ab) or its coincubation with an unlabeled probe containing the NF-κB binding sequence (cold probe) to compete with the labeled oligonucleotide. The results are one representative of more than three independent experiments. Primary astrocytes were pretreated with pyrrolidine dithiocarbamate (PTDC, NF-κB-specific inhibitor; 0–10 μm) for 30 min prior to their treatment with the recombinant LCN2 protein (10 μg/ml) or LPS (100 ng/ml) plus IFN-γ (50 units/ml) for 24 h (F). The concentration of nitrite in the culture media was measured by the Griess reagent. The results are the means ± S.D. (n = 3). *, p < 0.001 compared with the LCN2 or LPS/IFN-γ treatment alone. The astrocytes were pretreated with SC-514 (IKK-specific inhibitor, 10 μm) for 30 min prior to the treatment with the recombinant LCN2 protein (10 μg/ml) for 8–24 h. The expression of GFAP at mRNA or protein levels after 8 or 24 h was then assessed by RT-PCR or Western blot analysis, respectively (G).

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Expressing, Recombinant, Western Blot, Enzyme-linked Immunosorbent Assay, Labeling, Binding Assay, Sequencing, Concentration Assay, Reverse Transcription Polymerase Chain Reaction

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: Role of LCN2 in astrocyte migration and CXCL10 induction in cortical stab wound injury model. Cortical stab wound injury was performed with LCN2 wild-type (LCN2+/+) or LCN2-deficient mice (LCN2−/−) (A, upper). At 2 dpi, the mice were sacrificed, and cryosections were immunostained with antibodies against GFAP. The asterisk indicates stab wound injury site. The boxes indicate 200-μm × 200-μm squares placed for cell counting. Immunohistochemistry results showed that GFAP-positive cells in the peri-injury region were observed in both LCN2+/+ and LCN2−/− mice. A significant decrease in the number of GFAP-positive cells was observed in the immediate vicinity of injury site in LCN2−/− mice (A, lower panel). The results are one representative of more than three independent experiments. Scale bars, 200 μm. The values are the means ± S.D. from three different animals and six independent sections/animal. *, p < 0.05 compared with LCN2−/− mice in the same counting area; #, p < 0.05 between the values indicated. The mRNA levels of lcn2 (upper panel) and CXCL10 (lower panel) in LCN2+/+ and LCN2−/− mice were examined at 2 days after cortical stab wound injury (B). RNA was isolated from the injury site in the cortex and subjected to real time PCR. The injury-induced CXCL10 expression was completely abrogated in LCN2−/− brain as compared with LCN2+/+ littermates. GAPDH was used as a control in the real time PCR. The results are the means ± S.D. (n = 3). *, p < 0.05 compared with uninjured LCN2+/+ mice; **, p < 0.05 compared with injured LCN2+/+ mice; #, p < 0.05 compared with uninjured LCN2−/− mice.

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Migration, Cell Counting, Immunohistochemistry, Isolation, Real-time Polymerase Chain Reaction, Expressing, Control

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: Essential role of LCN2 in reactive astrocytosis and CXCL10 induction in LPS-induced mouse neuroinflammation models. LCN2+/+ or LCN2−/− were injected with LPS intracortically (A) or icv (B). After 2 dpi, the mice were sacrificed, and cryosections were immunostained with antibodies against LCN2 (green, upper) or GFAP (red, middle). The nuclei were counterstained with DAPI (blue, lower). The asterisk indicates the injection site. A significant decrease in both LCN2 and GFAP expression was observed in LCN2−/− mice. The results are one representative of more than three independent experiments. Scale bars, 100 μm. Quantification of the GFAP-positive cells was done in the cortex (A, upper graph) or hippocampus (B, upper graph). The values are the means ± S.D. from three different animals and five independent sections per animal. The mRNA levels of lcn2, CXCL10, and GFAP in LCN2+/+ and LCN2−/− mice were examined by real time PCR of cortical tissue around the injection site (A, lower graph) or hippocampus (B, lower graph) at 2 days after intracortical or icv injection with LPS, respectively. LCN2−/− mice exhibited markedly lower levels of CXCL10 and GFAP as compared with LCN2+/+ littermates. *, p < 0.05; compared with wild-type LPS-injected mice (LCN2+/+) at the same inflammation model. At 2 days after icv injection of LCN2+/+ mice with LPS, hippocampus was immunostained with antibodies against LCN2 (green) or GFAP (red) (C). The nuclei were counterstained with DAPI (blue). A merged image is shown in the lower right panel. The arrowheads indicate colocalization of LCN2 and GFAP (yellow). Cell bodies and processes of astrocytes in hippocampus were stained with LCN2 antibody. The results are representative of more than three independent experiments. Scale bars, 20 μm.

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Injection, Expressing, Real-time Polymerase Chain Reaction, Staining

Journal: The Journal of Biological Chemistry

Article Title: Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

doi: 10.1074/jbc.M111.299248

Figure Lengend Snippet: Schematic diagram depicting the promotion of CNS cell migration by LCN2-induced CXCL10 (A) and the possible pathway through which LCN2 induces astrocyte migration and morphological changes (B). A, LCN2 up-regulates CXCL10 expression in the multiple cell types in the CNS, such as astrocytes, microglia, neurons, and endothelial cells. Astrocyte-derived CXCL10 acts in a paracrine or autocrine manner to promote cell migration in the inflammatory scene. CXCL10 secreted by other cell types may play a similar role. The lcn2 receptor and CXCL10 receptor (CXCR3) are widely expressed in glia, endothelial cells, and neurons. B, LCN2 up-regulates CXCL10 and GFAP expression in reactive astrocytes through JAK2/STAT3 and NF-κB pathways. Although LCN2-up-regulated CXCL10 promotes cell migration, GFAP induction may lead to morphological changes observed in reactive astrocytosis. Based on the microarray analysis, LCN2 induces the up-regulation of IL-6 and down-regulation of PIAS3, thereby facilitating the STAT3 pathway (dotted line). NO production, downstream of the NF-κB, may cooperate with the STAT3 pathway to induce GFAP expression. NO has been shown to induce GFAP expression in astrocytes (bold dotted line) (54). Moreover, IL-6 previously induced GFAP expression through the STAT3 pathway (96). Other pathways may also participate in astrocyte migration and morphological change under the current conditions.

Article Snippet: The recombinant mouse CXCL10 protein (R & D Systems) was used as a standard.

Techniques: Migration, Expressing, Derivative Assay, Microarray