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P38? (MAPK14) critically regulates the immunological response and the production of specific cytokines and chemokines in astrocytes.

ABSTRACT: In CNS lesions, "reactive astrocytes" form a prominent cellular response. However, the nature of this astrocyte immune activity is not well understood. In order to study astrocytic immune responses to inflammation and injury, we generated mice with conditional deletion of p38? (MAPK14) in GFAP+ astrocytes. We studied the role of p38? signaling in astrocyte immune activation both in vitro and in vivo, and simultaneously examined the effects of astrocyte activation in CNS inflammation. Our results showed that specific subsets of cytokines (TNF?, IL-6) and chemokines (CCL2, CCL4, CXCL1, CXCL2, CXCL10) are critically regulated by p38? signaling in astrocytes. In an in vivo CNS inflammation model of intracerebral injection of LPS, we observed markedly attenuated astrogliosis in conditional GFAPcre p38?(-/-) mice. However, GFAPcre p38?(-/-) mice showed marked upregulation of CCL2, CCL3, CCL4, CXCL2, CXCL10, TNF?, and IL-1? compared to p38?fl/fl cohorts, suggesting that in vivo responses to LPS after GFAPcre p38? deletion are complex and involve interactions between multiple cell types. This finding was supported by a prominent increase in macrophage/microglia and neutrophil recruitment in GFAPcre p38?(-/-) mice compared to p38?fl/fl controls. Together, these studies provide important insights into the critical role of p38? signaling in astrocyte immune activation.

SUBMITTER: Lo U

PROVIDER: S-EPMC4264013 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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p38α (MAPK14) critically regulates the immunological response and the production of specific cytokines and chemokines in astrocytes.

Lo U U Selvaraj V V Plane J M JM Chechneva O V OV Otsu K K Deng W W

Scientific reports 20141212

In CNS lesions, "reactive astrocytes" form a prominent cellular response. However, the nature of this astrocyte immune activity is not well understood. In order to study astrocytic immune responses to inflammation and injury, we generated mice with conditional deletion of p38α (MAPK14) in GFAP+ astrocytes. We studied the role of p38α signaling in astrocyte immune activation both in vitro and in vivo, and simultaneously examined the effects of astrocyte activation in CNS inflammation. Our results ...[more]

PMID: 25502009

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Dataset Information

P38? (MAPK14) critically regulates the immunological response and the production of specific cytokines and chemokines in astrocytes.

Publications

p38α (MAPK14) critically regulates the immunological response and the production of specific cytokines and chemokines in astrocytes.

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