STAT3 regulates NF-kappaB recruitment to the IL-12p40 promoter in dendritic cells - PubMed (original) (raw)
. 2005 Jan 15;105(2):689-96.
doi: 10.1182/blood-2004-04-1309. Epub 2004 Jul 13.
Affiliations
- PMID: 15251981
- DOI: 10.1182/blood-2004-04-1309
Free article
STAT3 regulates NF-kappaB recruitment to the IL-12p40 promoter in dendritic cells
Frank Hoentjen et al. Blood. 2005.
Free article
Abstract
Interleukin-10-deficient (IL-10(-/-)) mice develop an IL-12-mediated intestinal inflammation in the absence of endogenous IL-10. The molecular mechanisms of the dysregulated IL-12 responses in IL-10(-/-) mice are poorly understood. In this study, we investigated the role of nuclear factor-kappa B (NF-kappaB) and signal transducers and activators of transcription 3 (STAT3) in lipopolysaccharide (LPS)-induced IL-12p40 gene expression in bone marrow derived-dendritic cells (BMDCs) isolated from wild-type (WT) and IL-10(-/-) mice. We report higher IL-12p40 mRNA accumulation and protein secretion in LPS-stimulated BMDCs isolated from IL-10(-/-) compared with WT mice. LPS-induced NF-kappaB signaling is similar in IL-10(-/-) and WT BMDCs as measured by IkappaBalpha phosphorylation and degradation, RelA phosphorylation and nuclear translocation, and NF-kappaB transcriptional activity, with no down-regulatory effects of exogenous IL-10. Chromatin immunoprecipitation demonstrated enhanced NF-kappaB (cRel, RelA) binding to the IL-12p40 promoter in IL-10(-/-) but not WT BMDCs. Interestingly, LPS induced STAT3 phosphorylation in WT but not IL-10(-/-) BMDCs, a process blocked by IL-10 receptor blocking antibody. Adenoviral gene delivery of a constitutively active STAT3 but not control green fluorescence protein (GFP) virus blocked LPS-induced IL-12p40 gene expression and cRel recruitment to the IL-12p40 promoter. In conclusion, dysregulated LPS-induced IL-12p40 gene expression in IL-10(-/-) mice is due to enhanced NF-kappaB recruitment to the IL-12p40 promoter in the absence of activated STAT3.
Similar articles
- Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice.
Kobayashi M, Kweon MN, Kuwata H, Schreiber RD, Kiyono H, Takeda K, Akira S. Kobayashi M, et al. J Clin Invest. 2003 May;111(9):1297-308. doi: 10.1172/JCI17085. J Clin Invest. 2003. PMID: 12727921 Free PMC article. - The guggulsterone derivative GG-52 inhibits NF-κB signaling in bone marrow-derived dendritic cells and attenuates colitis in IL-10 knockout mice.
Kang SJ, Kim JM, Koh SJ, Kim SH, Im JP, Jung HC, Kim JS. Kang SJ, et al. Life Sci. 2013 Jun 13;92(22):1064-71. doi: 10.1016/j.lfs.2013.04.003. Epub 2013 Apr 17. Life Sci. 2013. PMID: 23603141 - Interleukin 39: a new member of interleukin 12 family.
Lu Z, Xu K, Wang X, Li Y, Li M. Lu Z, et al. Cent Eur J Immunol. 2020;45(2):214-217. doi: 10.5114/ceji.2020.97911. Epub 2020 Jul 27. Cent Eur J Immunol. 2020. PMID: 33456334 Free PMC article. Review. - Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System.
Priester J, Dreute J, Kracht M, Schmitz ML. Priester J, et al. Biomedicines. 2022 Aug 29;10(9):2108. doi: 10.3390/biomedicines10092108. Biomedicines. 2022. PMID: 36140209 Free PMC article. Review.
Cited by
- Critical and independent role for SOCS3 in either myeloid or T cells in resistance to Mycobacterium tuberculosis.
Carow B, Reuschl AK, Gavier-Widén D, Jenkins BJ, Ernst M, Yoshimura A, Chambers BJ, Rottenberg ME. Carow B, et al. PLoS Pathog. 2013;9(7):e1003442. doi: 10.1371/journal.ppat.1003442. Epub 2013 Jul 4. PLoS Pathog. 2013. PMID: 23853585 Free PMC article. - IL-10 regulates Il12b expression via histone deacetylation: implications for intestinal macrophage homeostasis.
Kobayashi T, Matsuoka K, Sheikh SZ, Russo SM, Mishima Y, Collins C, deZoeten EF, Karp CL, Ting JP, Sartor RB, Plevy SE. Kobayashi T, et al. J Immunol. 2012 Aug 15;189(4):1792-9. doi: 10.4049/jimmunol.1200042. Epub 2012 Jul 11. J Immunol. 2012. PMID: 22786766 Free PMC article. - Immunoregulation of dendritic cells.
Wallet MA, Sen P, Tisch R. Wallet MA, et al. Clin Med Res. 2005 Aug;3(3):166-75. doi: 10.3121/cmr.3.3.166. Clin Med Res. 2005. PMID: 16160071 Free PMC article. Review. - Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells.
Ohtani M, Nagai S, Kondo S, Mizuno S, Nakamura K, Tanabe M, Takeuchi T, Matsuda S, Koyasu S. Ohtani M, et al. Blood. 2008 Aug 1;112(3):635-43. doi: 10.1182/blood-2008-02-137430. Epub 2008 May 20. Blood. 2008. PMID: 18492954 Free PMC article. - Nicotinic Acetylcholine Receptor Involvement in Inflammatory Bowel Disease and Interactions with Gut Microbiota.
Rueda Ruzafa L, Cedillo JL, Hone AJ. Rueda Ruzafa L, et al. Int J Environ Res Public Health. 2021 Jan 29;18(3):1189. doi: 10.3390/ijerph18031189. Int J Environ Res Public Health. 2021. PMID: 33572734 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous