| First Author | Yang Z | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 10 | Pages | 6205-13 |
| PubMed ID | 20937847 | Mgi Jnum | J:165637 |
| Mgi Id | MGI:4837954 | Doi | 10.4049/jimmunol.1000243 |
| Citation | Yang Z, et al. (2010) The Regulation of Th1 Responses by the p38 MAPK. J Immunol 185(10):6205-13 |
| abstractText | IL-12 is a dimeric cytokine that is produced primarily by APCs. In this study we examined the role that the p38 MAPKs (MAPK/p38) play in regulating IL-12 production. We show that inhibition of p38 dramatically increased IL-12 production upon stimulation, while decreasing TNF-alpha. This reciprocal effect on these two cytokines following MAPK/p38 inhibition occurred in many different APCs, following a variety of different stimuli. IL-12 production was also increased in macrophages treated with small interfering RNA to limit p38alpha expression, and in macrophages deficient in MKK3, a kinase upstream of p38. The increase in IL-12 production following MAPK/p38 inhibition appears to be due to enhanced IL-12 (p40) mRNA stability. We show that MAPK/p38 inhibition can promote Th1 immune responses and thereby enhance vaccine efficacy against leishmaniasis. In a mouse model of Leishmania major infection, vaccination with heat-killed L. major plus CpG and SB203580 elicited complete protection against infection compared with heat-killed L. major plus CpG without SB203580. Thus, this work suggests that MAPK/p38 inhibitors may be applied as adjuvants to bias immune responses and improve vaccinations against intracellular pathogens. |
