Involvement of STAT-1 and ets family members in interferon-gamma induction of CD40 transcription in microglia/macrophages
- PMID: 10823830
- DOI: 10.1074/jbc.M002482200
Involvement of STAT-1 and ets family members in interferon-gamma induction of CD40 transcription in microglia/macrophages
Abstract
Cluster of differentiation (CD)-40 is a cell surface receptor belonging to the tumor necrosis factor receptor family that plays a critical role in the regulation of immune responses. We have previously shown that the cytokine interferon (IFN)-gamma induces CD40 expression in microglia. Herein, we have elucidated the molecular mechanisms underlying IFN-gamma induction of CD40 gene expression in microglia/macrophages. IFN-gamma up-regulates CD40 expression at the transcriptional level, and this regulation involves the STAT-1alpha transcription factor. Microglia from STAT-1alpha-deficient mice were refractive to IFN-gamma induction of CD40 expression, illustrating the importance of STAT-1alpha in this response. Functional analysis of the CD40 promoter indicates that two gamma activated sequence elements as well as two Ets elements are involved in IFN-gamma induction of CD40 promoter activity. STAT-1alpha binds to the gamma activated sequence elements, whereas PU.1 and/or Spi-B bind to the Ets elements. The expression of PU.1 and Spi-B, in conjuction with STAT-1alpha activation, correlates with IFN-gamma inducibility of CD40 expression. Collectively, our data demonstrate the involvement of STAT-1alpha, PU.1, and Spi-B in IFN-gamma induction of CD40 gene expression in cells of the macrophage lineage.
Similar articles
-
IL-4-activated STAT-6 inhibits IFN-gamma-induced CD40 gene expression in macrophages/microglia.J Immunol. 2000 Dec 1;165(11):6235-43. doi: 10.4049/jimmunol.165.11.6235. J Immunol. 2000. PMID: 11086058
-
Suppressor of cytokine signaling 1 inhibits cytokine induction of CD40 expression in macrophages.J Immunol. 2002 Sep 1;169(5):2354-60. doi: 10.4049/jimmunol.169.5.2354. J Immunol. 2002. PMID: 12193701
-
Critical role of tumor necrosis factor-alpha and NF-kappa B in interferon-gamma -induced CD40 expression in microglia/macrophages.J Biol Chem. 2002 Apr 19;277(16):13796-803. doi: 10.1074/jbc.M111906200. Epub 2002 Feb 5. J Biol Chem. 2002. PMID: 11830590
-
Transcription factor PU.1 and immune cell differentiation (Review).Int J Mol Med. 2020 Dec;46(6):1943-1950. doi: 10.3892/ijmm.2020.4763. Epub 2020 Oct 21. Int J Mol Med. 2020. PMID: 33125129 Review.
-
Leishmania intercepts IFN-γR signaling at multiple levels in macrophages.Cytokine. 2022 Sep;157:155956. doi: 10.1016/j.cyto.2022.155956. Epub 2022 Jul 1. Cytokine. 2022. PMID: 35785668 Review.
Cited by
-
All trans-retinoic acid protects against acute ischemic stroke by modulating neutrophil functions through STAT1 signaling.J Neuroinflammation. 2019 Aug 31;16(1):175. doi: 10.1186/s12974-019-1557-6. J Neuroinflammation. 2019. PMID: 31472680 Free PMC article.
-
Regulation of signal transducer and activator of transcription and suppressor of cytokine-signaling gene expression in the brain of mice with astrocyte-targeted production of interleukin-12 or experimental autoimmune encephalomyelitis.Am J Pathol. 2002 Jan;160(1):271-88. doi: 10.1016/S0002-9440(10)64371-4. Am J Pathol. 2002. PMID: 11786421 Free PMC article.
-
Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population.Am J Hum Genet. 2012 Oct 5;91(4):721-8. doi: 10.1016/j.ajhg.2012.08.010. Epub 2012 Sep 20. Am J Hum Genet. 2012. PMID: 23000144 Free PMC article.
-
Cytokines involved in interferon-gamma production by human macrophages.J Innate Immun. 2010;2(1):56-65. doi: 10.1159/000247156. Epub 2009 Oct 10. J Innate Immun. 2010. PMID: 20375623 Free PMC article.
-
Adipocyte-Specific Ablation of PU.1 Promotes Energy Expenditure and Ameliorates Metabolic Syndrome in Aging Mice.Front Aging. 2022 Feb 2;2:803482. doi: 10.3389/fragi.2021.803482. eCollection 2021. Front Aging. 2022. PMID: 35822007 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
Miscellaneous