IL-1β induces human mesangial cell injury via exacerbating lipid-induced endoplasmic reticulum stress |
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Authors: | SHI Jing CUI Jing-jing YANG Hai-ping LIU Wei WAN Jun-li WANG Zhi-tie QIU Gui-xia LI Qiu |
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Affiliation: | 1.Department of Nephroimmunology,2Immunology Section of Pediatric Institute, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China. |
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Abstract: | AIM:To investigate the molecular mechanism that interleukin-1 beta (IL-1β) exacerbates lipid-induced endoplasmic reticulum stress (ERS) and the injury of human mesangial cells (HMCs). METHODS:HMCs were cultured and divided into control group, low-density lipoprotein (LDL) group, IL-1β+LDL group and 4-phenyl butyric acid (4-PBA)+IL-1β+LDL group. Oil red O staining was used to evaluate the accumulation of lipid droplet in the cells. The mRNA levels of glucose-regulated protein 78(GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK) and α-smooth muscle actin (α-SMA) were examined by real-time PCR. Immunocytochemistry was used to observe GRP78 expression. The protein level of NF-κB p65 was measured by Western blotting. The releases of IL-6 and TGF-β1 in the culture supernatants of HMCs were detected by ELISA. RESULTS:Compared with LDL group, the intracellular lipid accumulation, the mRNA levels of GRP78 and PERK, the protein expression of GRP78 and NF-κB p65, and the release of IL-6 were significantly increased in IL-1β+LDL group. Dramatically reduced intracellular lipid accumulation, down-regulated GRP78 and PERK mRNA expression, decreased protein levels of GRP78 and NF-κB p65, and suppressed IL-6 release were observed in 4-PBA+IL-1β+LDL group as compared with IL-1β+LDL group. The mRNA level of α-SMA was higher in IL-1β+LDL group than that in LDL group, and that in 4-PBA+IL-1β+LDL group was significantly depressed. CONCLUSION:IL-1β exacerbates lipid-induced ERS, thus promoting the injury of HMCs. |
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Keywords: | Inflammation Mesangial cells Lipid accumulation Endoplasmic reticulum stress |
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