| First Author | Xing B | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 2 | Pages | e56852 |
| PubMed ID | 23457629 | Mgi Jnum | J:198281 |
| Mgi Id | MGI:5496298 | Doi | 10.1371/journal.pone.0056852 |
| Citation | Xing B, et al. (2013) Deficiency in p38beta MAPK fails to inhibit cytokine production or protect neurons against inflammatory insult in in vitro and in vivo mouse models. PLoS One 8(2):e56852 |
| abstractText | The p38 MAPK pathway plays a key role in regulating the production of proinflammatory cytokines, such as TNFalpha and IL-1beta, in peripheral inflammatory disorders. There are four major isoforms of p38 MAPK (p38alpha, beta, delta, gamma), with p38alpha and p38beta the targets of most p38 MAPK inhibitor drugs. Our previous studies demonstrated that the p38alpha MAPK isoform is an important contributor to stressor-induced proinflammatory cytokine up-regulation and neurotoxicity in the brain. However, the potential role of the p38beta MAPK isoform in CNS proinflammatory cytokine overproduction and neurotoxicity is poorly understood. In the current studies, we used primary microglia from wild type (WT) and p38beta knockout (KO) mice in co-culture with WT neurons, and measured proinflammatory cytokines and neuron death after LPS insult. We also measured neuroinflammatory responses in vivo in WT and p38beta KO mice after administration of LPS by intraperitoneal or intracerebroventricular injection. WT and p38beta KO microglia/neuron co-cultures showed similar levels of TNFalpha and IL-1beta production in response to LPS treatment, and no differences in LPS-induced neurotoxicity. The in vitro results were confirmed in vivo, where levels of TNFalpha and IL-1beta in the CNS were not significantly different between WT or p38beta KO mice after LPS insult. Our results suggest that, similar to peripheral inflammation, p38alpha is critical but p38beta MAPK is dispensable in the brain in regards to proinflammatory cytokine production and neurotoxicity induced by LPS inflammatory insult. |
