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.

Keywords: Inflammatory response; Peptidoglycan; TLR1/TLR2; mTOR.