The effects of TNF-α and IL-13 on the generation of collagen in Human Hepatic Stellate Cell

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  Background: IL-13 which is produced by a variety of cells, mainly by activated type Ⅱ T helper cells, is a multi-effectiveness of cytokines.It has confirmed that IL-13 is the primary cytokine that induces fibrosis, with IL-13 receptor alpha 1 (IL-13Rαl) combining to produce a fibrogenic role.In addition, IL-13 receptor alpha 2 (IL-13Rα2) is another receptor ofIL-13 and its competitive inhibition of the combination ofIL-13Rα1 and IL-13 can result in the interruption of the JAK/STAT signal transduction pathway which would mediates the fibrogenic process.Tumor necrosis factor-alpha (TNF-α) is a mononuclear factor which is produced mainly by monocytes/phagocytic cells with broad biological activity.TNF-α can inhibit the expression of TGF-β1 which promotes fibrosis.Recent studies have found that TNF-α can up-regulate the expression of IL-13Rα2 in the fibroblasts of lung and skin, which would inhibit the signal transduction pathway of IL-13-mediated fibrosis.In this study, we will investigate whether IL-13Rα2 expresses in human hepatic stellate cell line LX-2, and whether TNF-α can up-regulate the expression of IL-13Rα2, which would inhibit the synthesis of collagen in LX-2 cells.Methods: ① Modality of LX-2 cells were observed by HE staining ; ② LX-2 cells were stimulated with TNF-α and IL-13 in different doses and with different time points ; ③ The expression of IL-13Rα 1 and IL-13Rα2 mRNA were evaluated by RT-PCR ; ④ The expression of PCOL Ⅰ mRNA was evaluated after LX-2 cells were stimulated with TNF-α and IL-13.First, LX-2 cells were stimulated with TNF-α and IL-13 in different doses and with different time points.The expression of PCOL Ⅰ mRNA were evaluated by RT-PCR.Second, LX-2 cells were cultured and divided into four groups: control group, TNF-α group, IL-13 group and TNF-α+ IL-13 group.The expression of PCOL Ⅰ mRNA was evaluated by RT-PCR ; ⑤ The expression of PCOL Ⅰ protein was evaluated by immunohistochemisty ; ⑥ The collagen content was evaluated by hydroxyproline assay.Results: ① The activity of LX-2 cells were well, and TNF-α and IL-13 were no toxicity to LX-2 cells ; ② RT-PCR results showed that IL-13Rαl mRNA was expressed in any doses of TNF-α and IL-13 at any time point.TNF-α and IL-13 had no effection on the expression of IL-13Rαl mRNA in LX-2 cells.And IL-13Rα2 was not expressed in LX-2 cells ; ③ RTPCR results showed that TNF-α could down-regulate the expression of PCOL Ⅰ mRNA in LX-2 cells, which was negatively correlated with dose.IL-13 could up-regulate the expression of PCOL Ⅰ mRNA in LX-2 cells in different doses.The expression of PCOL Ⅰ mRNA in LX-2 cells was up-regulated most significantly in 50ng/ml group ; ④ The results of immunohistochemisty demonstrated that the expression of PCOL Ⅰ protein is consistent with the result of RT-PCR ; ⑤ The results of hydroxyproline assay demonstrated that the expression of collagen is consistent with the result of RT-PCR.Conclusions: ① TNF-α and IL-13 have no effection on the expression of IL-13Rα 1 mRNA in LX-2 cells ; ② TNF-α can down-regulate the expression of PCOL Ⅰ with the dosedependent in LX-2 cells ; ③ IL-13 can be different degrees up-regulate the expression of PCOL Ⅰ in LX-2 cells ; ④ There is no expression of IL-13Rα2 in LX-2 cells .
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