The transcription factor cMaf is targeted by mTOR, and regulates the inflammatory response via the TLR4 signaling pathway

Wang,Yan; Luan,Caifu; Zhang,Guili; Sun,Chengming

doi:10.3892/ijmm.2018.3510

The transcription factor cMaf is targeted by mTOR, and regulates the inflammatory response via the TLR4 signaling pathway

Authors:
- Yan Wang
- Caifu Luan
- Guili Zhang
- Chengming Sun
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Affiliations: Clinical Laboratory, Shanghai Pudong New District Zhoupu Hospital, Shanghai 201318, P.R. China, Clinical Laboratory, Yantai Yuhuangding Hospital, Yantai, Shandong 370600, P.R. China
Published online on: February 23, 2018 https://doi.org/10.3892/ijmm.2018.3510
Pages: 2935-2942

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Abstract

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.

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