Open AccessThe transcription factor cMaf is targeted by mTOR, and regulates the inflammatory response via the TLR4 signaling pathway
Author(s) -
Yan Wang,
Caifu Luan,
Guili Zhang,
Chengming Sun
Publication year - 2018
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2018.3510
Subject(s) - pi3k/akt/mtor pathway , biology , gene knockdown , signal transduction , ribosomal s6 kinase , microbiology and biotechnology , transcription factor , kinase , small interfering rna , cancer research , ribosomal protein s6 , p70 s6 kinase 1 , apoptosis , transfection , cell culture , gene , biochemistry , genetics
cMaf is a leucine-zipper transcription factor that is involved in cell differentiation, oncogenic transformation, and human diseases; however, the functions of cMaf in inflammatory responses in macrophages are still not fully understood. Western blot analysis showed that cMaf expression was induced by lipopolysaccharide (LPS) stimulation in mouse macrophages. An enzyme-linked immunosorbent assay was performed to detect the level of expression of inflammatory cytokines after knockdown of cMaf expression in macrophages using a small interfering RNA (siRNA). Signaling pathway inhibitor analyses indicated that extracellular signal-related kinase and phosphoinositide 3-kinase contribute to mammalian target of rapamycin phosphorylation (mTOR), which controls cMaf expression at the translational level by regulating the expression of eIF4E-binding protein 1 and S6 ribosomal kinase 1 in response to Toll-like receptor 4 signaling. Histopathological findings of the lung and a survival analysis showed that mice transplanted with cMaf-knockdown macrophages were more susceptible to LPS challenge. Taken together, our study revealed that the control of cMaf expression at the translational level by mTOR regulated the expression of inflammatory genes in response to LPS challenge. Moreover, cMaf protected mice from septic shock indicating that cMaf may improve host fitness, thereby enabling the survival of certain infectious diseases.