Unknown

Dataset Information

0

P38? senses environmental stress to control innate immune responses via mechanistic target of rapamycin.

ABSTRACT: The MAPK p38? senses environmental stressors and orchestrates inflammatory and immunomodulatory reactions. However, the molecular mechanism how p38? controls immunomodulatory responses in myeloid cells remains elusive. We found that in monocytes and macrophages, p38? activated the mechanistic target of rapamycin (mTOR) pathway in vitro and in vivo. p38? signaling in myeloid immune cells promoted IL-10 but inhibited IL-12 expression via mTOR and blocked the differentiation of proinflammatory CD4(+) Th1 cells. Cellular stress induced p38?-mediated mTOR activation that was independent of PI3K but dependent on the MAPK-activated protein kinase 2 and on the inhibition of tuberous sclerosis 1 and 2, a negative regulatory complex of mTOR signaling. Remarkably, p38? and PI3K concurrently modulated mTOR to balance IL-12 and IL-10 expression. Our data link p38? to mTOR signaling in myeloid immune cells that is decisive for tuning the immune response in dependence on the environmental milieu.

SUBMITTER: Katholnig K 

PROVIDER: S-EPMC3563859 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

p38α senses environmental stress to control innate immune responses via mechanistic target of rapamycin.

Katholnig Karl K   Kaltenecker Christopher C CC   Hayakawa Hiroko H   Rosner Margit M   Lassnig Caroline C   Zlabinger Gerhard J GJ   Gaestel Matthias M   Müller Mathias M   Hengstschläger Markus M   Hörl Walter H WH   Park Jin Mo JM   Säemann Marcus D MD   Weichhart Thomas T  

Journal of immunology (Baltimore, Md. : 1950) 20130111 4

The MAPK p38α senses environmental stressors and orchestrates inflammatory and immunomodulatory reactions. However, the molecular mechanism how p38α controls immunomodulatory responses in myeloid cells remains elusive. We found that in monocytes and macrophages, p38α activated the mechanistic target of rapamycin (mTOR) pathway in vitro and in vivo. p38α signaling in myeloid immune cells promoted IL-10 but inhibited IL-12 expression via mTOR and blocked the differentiation of proinflammatory CD4(  ...[more]

Similar Datasets

Unknown Mechanistic Target of Rapamycin Pathway in Epileptic Disorders.
| S-EPMC6514310 | biostudies-literature
Unknown Mechanistic understanding of innate and adaptive immune responses in SARS-CoV-2 infection.
| S-EPMC8084627 | biostudies-literature
Unknown Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases.
| S-EPMC5314913 | biostudies-other
Unknown Aberrant Activation of p38 MAP Kinase-Dependent Innate Immune Responses Is Toxic to Caenorhabditis elegans.
| S-EPMC4777117 | biostudies-literature
Unknown Gene Expression Control by Glucocorticoid Receptors during Innate Immune Responses.
| S-EPMC4835445 | biostudies-literature
Unknown Identification of mechanically regulated phosphorylation sites on tuberin (TSC2) that control mechanistic target of rapamycin (mTOR) signaling.
| S-EPMC5409467 | biostudies-literature
Unknown Labor inhibits placental mechanistic target of rapamycin complex 1 signaling.
| S-EPMC4270912 | biostudies-literature
Unknown Mechanistic target of rapamycin signaling in mouse models of accelerated aging.
| S-EPMC6909891 | biostudies-literature
Unknown Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2).
| S-EPMC3868844 | biostudies-literature
Unknown Mechanistic target of rapamycin complex 2 protects the heart from ischemic damage.
| S-EPMC4131547 | biostudies-literature