Title
Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3 (Mkk3)-deficient mice
UMMS Affiliation
Graduate School of Biomedical Sciences; Howard Hughes Medical Institute and Section of Immunobiology; Program in Molecular Medicine
Publication Date
1999-04-15
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
The p38 mitogen-activated protein kinase (MAPK) pathway, like the c-Jun N-terminal kinase (JNK) MAPK pathway, is activated in response to cellular stress and inflammation and is involved in many fundamental biological processes. To study the role of the p38 MAPK pathway in vivo, we have used homologous recombination in mice to inactivate the Mkk3 gene, one of the two specific MAPK kinases (MAPKKs) that activate p38 MAPK. Mkk3(-/-) mice were viable and fertile; however, they were defective in interleukin-12 (IL-12) production by macrophages and dendritic cells. Interferon-gamma production following immunization with protein antigens and in vitro differentiation of naive T cells is greatly reduced, suggesting an impaired type I cytokine immune response. The effect of the p38 MAPK pathway on IL-12 expression is at least partly transcriptional, since inhibition of this pathway blocks IL-12 p40 promoter activity in macrophage cell lines and IL-12 p40 mRNA is reduced in MKK3-deficient mice. We conclude that the p38 MAP kinase, activated through MKK3, is required for the production of inflammatory cytokines by both antigen-presenting cells and CD4(+) T cells.
DOI of Published Version
10.1093/emboj/18.7.1845
Source
EMBO J. 1999 Apr 1;18(7):1845-57. Link to article on publisher's site
Journal/Book/Conference Title
The EMBO journal
Related Resources
PubMed ID
10202148
Repository Citation
Lu H, Yang DD, Wysk MA, Gatti E, Mellman I, Davis RJ, Flavell RA. (1999). Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3 (Mkk3)-deficient mice. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1093/emboj/18.7.1845. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/783