Mechanism of HMGB-1-induced inflammatory response in human bronchial epithelial cells
- Author:
- No author available
- Journal Title:
- Chinese Journal of Biomedical Engineering
- Issue:
- 1
- DOI:
- 10.3760/cma.j.issn.1674-1927.2018.01.002
- Key Word:
- HMGB-1;NHBE;炎性反应;RAGE;JNK;NF-κB;HMGB-1;NHBE;Inflammation;RAGE;JNK;NF-κB
Abstract： Objective To investigate the mechanism of extracellular high mobility group box 1 (HMGB-1)-induced inflammatory response in normal human bronchial epithelial cells(NHBE). Methods The subjects were divided into the control group,HMGB-1 group,HMGB-1+RAGE antibody(RAGE-Ab) group,HMGB-1+JNK inhibitor SP600125 group,and RAGE-Ab group. Immunofluorescence technique was used to analyze the expression of RAGE protein. ELISA assay was used to determine the levels of inflammatory cytokines TNF-α,IL-8,IL-10 and MCP-1 in NHBE cell supernatant. Western blotting was used to analyze the expression of RAGE,p-JNK and p-NF-κB p65 protein. Results HMGB-1 could dose-dependently induce RAGE protein expression. HMGB- 1 could significantly increase the intensity of fluorescence at the concentrations of 5 and 10μg/ml compared with that in the control group(P<0.05). The RAGE expression decreased significantly in the HMGB-1+RAGE-Ab group(P<0.05),whereas there was no significant change in RAGE protein expression in the HMGB-1+SP600125 group. Compared with the blank control group,the levels of TNF-α,IL-8,IL-10,and MCP-1 significantly increased after the treatment with HMGB-1(P<0.05). The release of inflammatory factors significantly decreased in the HMGB-1+RAGE-Ab group and HMGB-1+SP600125 group (P<0.05). Compared with the blank control group,the protein expression of RAGE,p-JNK and p-NF-κB p65 dose-dependently increased after the treatment of NHBE cells with HMGB-1(P<0.05). The protein expression of RAGE,p-JNK and p-NF-κB p65 in the HMGB-1+RAGE-Ab group significantly decreased(P<0.05). The protein expression of p-JNK and p-NF-κB p65 in the HMGB-1+SP600125 group significantly decreased (P<0.05),whereas there was no significant change in the expression of RAGE. Conclusion The inflammatory response induced by HMGB-1 in the NHBE cells is mediated through the RAGE/JNK/NF-κB signaling pathway.
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