title: mTORC1 mediates peptidoglycan induced inflammatory cytokines expression and NF-κB activation in macrophages.
abstract: Peptidoglycan (PGN) is the major structural component of the bacterial cell wall, especially gram positive bacteria, which induces inflammatory responses. Mammalian target of rapamycin (mTOR) regulates the production of inflammatory cytokines induced by antigens, while the function of mTORC1 in peptidoglycan induced inflammatory response is unknown. This study aims to examine the role and the regulatory mechanism of mTOR signaling pathway in peptidoglycan induced cytokine expression in mouse macrophages. We observed that peptidoglycan upregulated the secretion of proinflammatory cytokines IL-6, TNF-α and anti-inflammatory cytokine IL-10 in a dose- and time-dependent manner. mTORC1 positively regulates IL-6 and TNF-α, but negatively regulates IL-10 secretion. mTORC1 regulates NF-κB p65 activation by degrading IκB-α in response to peptidoglycan. mTOR, NF-κB and STAT3 signaling pathways are involved in peptidoglycan induced inflammatory cytokines expression via a TLR1/TLR2-dependent mechanism in macrophages. Thus, mTORC1 pathway regulates the innate immune response to bacterial peptidoglycan.
authors.affiliation: College of Life Science, Inner Mongolia University, Hohhot, China; School of Medicine, Mongolian National University of Medical Sciences, Ulan Bator, Mongolia.
authors.forename: Nyamtsengel
authors.initials: N
authors.lastname: Vangan
authors.affiliation: Inner Mongolia People's Hospital, Hohhot, China.
authors.forename: Yinfang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: College of Life Science, Inner Mongolia University, Hohhot, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Jia
authors.affiliation: College of Life Science, Inner Mongolia University, Hohhot, China.
authors.forename: Wenlei
authors.initials: W
authors.lastname: Bao
authors.affiliation: College of Life Science, Inner Mongolia University, Hohhot, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Life Science, Inner Mongolia University, Hohhot, China.
authors.forename: Qiburi
authors.initials: Q
authors.lastname: He
authors.affiliation: College of Life Science, Inner Mongolia University, Hohhot, China.
authors.forename: Uyanga
authors.initials: U
authors.lastname: Binderiya
authors.affiliation: College of Life Science, Inner Mongolia University, Hohhot, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Feng
authors.affiliation: College of Life Science, Inner Mongolia University, Hohhot, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: College of Life Science, Inner Mongolia University, Hohhot, China. Electronic address: haohf@life.imu.edu.cn.
authors.forename: Huifang
authors.initials: H
authors.lastname: Hao
authors.affiliation: College of Life Science, Inner Mongolia University, Hohhot, China. Electronic address: lswzg@imu.edu.cn.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D015870:Gene Expression; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010457:Peptidoglycan / Q000276:immunology* / Q000302:isolation & purification; D013211:Staphylococcus aureus / Q000737:chemistry / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D016207:Cytokines; D046912:Multiprotein Complexes; D016328:NF-kappa B; D010457:Peptidoglycan; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Inflammatory response; Peptidoglycan; TLR1/TLR2; mTOR