| First Author | Risco A | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 28 | Pages | 11200-5 |
| PubMed ID | 22733747 | Mgi Jnum | J:186404 |
| Mgi Id | MGI:5432279 | Doi | 10.1073/pnas.1207290109 |
| Citation | Risco A, et al. (2012) p38gamma and p38delta kinases regulate the Toll-like receptor 4 (TLR4)-induced cytokine production by controlling ERK1/2 protein kinase pathway activation. Proc Natl Acad Sci U S A 109(28):11200-5 |
| abstractText | On the basis mainly of pharmacological experiments, the p38alpha MAP kinase isoform has been established as an important regulator of immune and inflammatory responses. However, the role of the related p38gamma and p38delta kinases has remained unclear. Here, we show that deletion of p38gamma and p38delta impaired the innate immune response to lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) ligand, by blocking the extracellular signal-regulated kinase 1/2 (ERK1/2) activation in macrophages and dendritic cells. p38gamma and p38delta were necessary to maintain steady-state levels of tumor progression locus 2 (TPL2), the MKK kinase that mediates ERK1/2 activation after TLR4 stimulation. TNFalpha, IL-1beta, and IL-10 production were reduced in LPS-stimulated macrophages from p38gamma/delta-null mice, whereas IL-12 and IFNbeta production increased, in accordance with the known effects of TPL2/ERK1/2 signaling on the induction of these cytokines. Furthermore, p38gamma/delta-deficient mice were less sensitive than controls to LPS-induced septic shock, showing lower TNFalpha and IL-1beta levels after challenge. Together, our results establish p38gamma and p38delta as key components in innate immune responses. |
