The Role of IL-35 in the Pathophysiological Processes of Liver Disease.

It is known that liver diseases have several characteristics of massive lipid accumulation and lipid metabolic disorder, and are divided into liver inflammation, liver fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in patients. Interleukin (IL)-35, a new-discovered cytokine, can protect the liver from the environmental attack by increasing the ratio of Tregs (T regulatory cells) which can increase the anti-inflammatory cytokines and inhibit the proliferation of immune cellular. Interestingly, two opposite mechanisms (pro-inflammatory and anti-inflammatory) have connection with the ultimate formation of liver diseases, which suggest that IL-35 may play crucial function in the process of liver diseases through immunosuppressive regulation. Besides, some obvious advantages also imply that IL-35 can be considered as a new therapeutic target to control the progression of liver diseases, while its mechanism of function still needs further research.

TMEM100 mediates inflammatory cytokines secretion in hepatic stellate cells and its mechanism research.

Recent studies have shown that Transmembrane protein 100 (TMEM100) is a gene at locus 17q32 encoding a 134-amino acid protein with two hypothetical transmembrane domainsa, and first identified as a transcript from the mouse genome. As a downstream target gene of bone morphogenetic protein (BMP)-activin receptor-like kinase 1 (ALK1) signaling, it was activated to participate in inducing arterial endothelium differentiation, maintaining vascular integrity, promoting cell apoptosis, inhibiting metastasis and proliferation of cancer cells. However, evidence for the function of TMEM100 in inflammation is still limited. In this study, we explore the role of TMEM100 in inflammatory cytokine secretion and the role of MAPK signaling pathways in tumor necrosis factor-alpha (TNF-α)-induced TMEM100 expression in LX-2 cells. We found that the expression of TMEM100 was decreased markedly in human liver fibrosis tissues, and its expression was also inhibited in LX-2 cells induced by TNF-α, suggesting that it might be associated with the development of inflammation. Therefore, we demonstrated that overexpression of TMEM100 by transfecting pEGFP-C2-TMEM100 could lead to the down-regulation of IL-1ß and IL-6 secretion. Moreover, we found that expression changes of TMEM100 could be involved in inhibition or activation of MAPK signaling pathways accompanied with regulating phosphorylation levels of ERK and JNK protein in response to TNF-α. These results suggested that TMEM100 might play an important role in the secretion of inflammatory cytokines (IL-1ß and IL-6) of LX-2 cells induced by TNF-α, and MAPK (ERK and JNK) signaling pathways might participate in its induction of expression.