| First Author | Lo U | Year | 2014 |
| Journal | Sci Rep | Volume | 4 |
| Pages | 7405 | PubMed ID | 25502009 |
| Mgi Jnum | J:250680 | Mgi Id | MGI:6102099 |
| Doi | 10.1038/srep07405 | Citation | Lo U, et al. (2014) p38alpha (MAPK14) critically regulates the immunological response and the production of specific cytokines and chemokines in astrocytes. Sci Rep 4:7405 |
| abstractText | 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 p38alpha (MAPK14) in GFAP+ astrocytes. We studied the role of p38alpha 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 (TNFalpha, IL-6) and chemokines (CCL2, CCL4, CXCL1, CXCL2, CXCL10) are critically regulated by p38alpha signaling in astrocytes. In an in vivo CNS inflammation model of intracerebral injection of LPS, we observed markedly attenuated astrogliosis in conditional GFAPcre p38alpha(-/-) mice. However, GFAPcre p38alpha(-/-) mice showed marked upregulation of CCL2, CCL3, CCL4, CXCL2, CXCL10, TNFalpha, and IL-1beta compared to p38alphafl/fl cohorts, suggesting that in vivo responses to LPS after GFAPcre p38alpha 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 p38alpha(-/-) mice compared to p38alphafl/fl controls. Together, these studies provide important insights into the critical role of p38alpha signaling in astrocyte immune activation. |
