TMEM9 mediates IL-6 and IL-1β secretion and is modulated by the Wnt pathway

Novel studies have shown that the Transmembrane protein 9 (TMEM9) gene is localized at 1q41 and encodes a protein consisting of 183 amino acids with an N-terminus containing many important domains. As a novel human transmembrane protein, TMEM9 is highly conserved in species from Caenorhabditis elegans to humans and is widely expressed in many tissues and cells. Moreover, TMEM9 may play an important role in intracellular transport and the growth of hepatoma cells. However, evidence for the function of TMEM9 in inflammation is still limited. We studied the expression of TMEM9 and its effect on cytokine secretion in tumor necrosis factor-alpha (TNF-α)-induced LX-2 cells. We proved that overexpression of TMEM9 by transfection with pEGFP-C2-TMEM9 may increase the expression of IL-6 and IL-1β in LX-2 cells. At the same time, knockdown of TMEM9 expression by transfection with a TMEM9-siRNA decreased IL-6 and IL-1β secretion in LX-2 cells. Additionally, our results proved that overexpression of TMEM9 enhanced the protein expression levels of the canonical Wnt/β-catenin accompanied by an upregulation of wnt2b, wnt3a and β-catenin protein levels in LX-2 cells treated with TNF-α. These results indicate that TMEM9 plays a significant role in TNF-α-enhanced cytokines (IL-6 and IL-1β) secretion in LX-2 cells and that the canonical Wnt/β-catenin signaling pathway is involved in the induction of these cytokine expressions.