Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses.

Isoliquiritigenin protects against sepsis- induced lung and liver injury by reducing inflammatory responses.Ĭhen, Xiong Cai, Xueding Le, Rongrong Zhang, Man Gu, Xuemei Shen, Feixia Hong, Guangliang Chen, Zimiao Copyright Â© 2018 by The American Association of Immunologists, Inc. The present study thus demonstrates that MTOR serves as an early adaptive signal that suppresses the PM- induced necroptosis, NFKB activation, and inflammatory response in lung macrophages, and suggests that activation of MTOR or inhibition of necroptosis in macrophages may represent novel therapeutic strategies for PM-related airway disorders. Inhibition of necroptosis or NFKB pathways significantly ameliorated PM- induced inflammatory response in MTOR-deficient macrophages. Mechanistically, PM activated MTOR through modulation of ERK, AKT serine/threonine kinase 1, and tuberous sclerosis complex signals, whereas MTOR deficiency further enhanced the PM- induced necroptosis and activation of subsequent NF Îº light-chain-enhancer of activated B cells (NFKB) signaling. Pharmacological inhibition or genetic knockdown of MTOR in bone marrow-derived macrophages leads to an amplified cytokine production upon PM exposure, and mice with specific knockdown of MTOR or ras homolog enriched in brain in myeloid cells exhibit significantly aggregated airway inflammation. We observed that coarse PM treatment rapidly activated mechanistic target of rapamycin (MTOR) in mouse alveolar macrophages in vivo, and in cultured mouse bone marrow-derived macrophages, mouse peritoneal macrophages, and RAW264.7 cells. However, the detailed mechanisms of inflammatory responses induced by PM exposure in macrophages are still unclear. Alveolar macrophages represent a major type of innate immune responses to foreign substances. Increasing toxicological and epidemiological studies have demonstrated that ambient particulate matter (PM) could cause adverse health effects including inflammation in the lung. Li, Zhouyang Wu, Yinfang Chen, Hai-Pin Zhu, Chen Dong, Lingling Wang, Yong Liu, Huiwen Xu, Xuchen Zhou, Jiesen Wu, Yanping Li, Wen Ying, Songmin Shen, Huahao Chen, Zhi-Hua MTOR Suppresses Environmental Particle- Induced Inflammatory Response in Macrophages. Regular training may enhance immune competence, whereas trauma- induced SIRS often paves the way for infectious complications, such as sepsis. Intermittent states of rest, as well as anti-oxidant capacity, are lacking or minor in trauma but are high in exercising individuals. Exercise leads to a balanced equilibrium between inflammatory and anti- inflammatory responses. Different anti- inflammatory cytokines may be involved in the control of inflammation in trauma- and exercise- induced stress. Inflammatory cytokines are common denominators in both trauma and exercise, although there are marked quantitative differences. Exercise-related SIRS is conditioned by hyperthermia and concomitant heat shock responses, whereas trauma- induced SIRS manifests concomitantly with tissue necrosis and immune activation, secondarily followed by fever. Trauma- induced systemic inflammatory response versus exercise- induced immunomodulatory effects.Īccidental trauma and heavy endurance exercise, both induce a kind of systemic inflammatory response, also called systemic inflammatory response syndrome (SIRS).

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