Protection by mTOR Inhibition on Zymosan-Induced Systemic Inflammatory Response and Oxidative/Nitrosative Stress: Contribution of mTOR/MEK1/ERK1/2/IKKβ/IκB-α/NF-κB Signalling Pathway.

Mammalian target of rapamycin (mTOR), a serine/threonine kinase regulate variety of cellular functions including cell growth, differentiation, cell survival, metabolism, and stress response, is now appreciated to be a central regulator of immune responses. Because mTOR inhibitors enhanced the anti-inflammatory activities of regulatory T cells and decreased the production of proinflammatory cytokines by macrophages, mTOR has been a pharmacological target for inflammatory diseases. In this study, we examined the role of mTOR in the production of proinflammatory and vasodilator mediators in zymosan-induced non-septic shock model in rats.

Activation of mTOR/IκB-α/NF-κB pathway contributes to LPS-induced hypotension and inflammation in rats.

Mammalian target of rapamycin (mTOR), a serine/threonine kinase plays an important role in various pathophysiological processes including cancer, metabolic diseases, and inflammation. Although mTOR participates in Toll-like receptor 4 signalling in different cell types, the role of this enzyme in sepsis pathogenesis and its effects on hypotension and inflammation in endotoxemic rats remains unclear. In this study we investigated the effects of mTOR inhibition on lipopolysaccharide (LPS)-induced changes on expressions and/or activities of ribosomal protein S6 (rpS6), an mTOR substrate, nuclear factor-κB (NF-κB) p65, inhibitor κB (IκB)-α, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 with production of nitric oxide, peroxynitrite, prostacyclin, and tumor necrosis factor (TNF)-α and activity of myeloperoxidase (MPO), which results in hypotension and inflammation.