The AP-1 Transcription Factor c-Jun Promotes Arthritis by Regulating Cyclooxygenase-2 and Arginase-1 Expression in Macrophages

Hannemann N, Jordan J, Paul S, Reid S, Baenkler HW, Sonnewald S, Bäuerle T, Vera J, Schett G, Bozec A (2017)


Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 198

Pages Range: 3605-3614

Journal Issue: 9

DOI: 10.4049/jimmunol.1601330

Abstract

Activation of proinflammatory macrophages is associated with the inflammatory state of rheumatoid arthritis. Their polarization and activation are controlled by transcription factors such as NF-?B and the AP-1 transcription factor member c-Fos. Surprisingly, little is known about the role of the AP-1 transcription factor c-Jun in macrophage activation. In this study, we show that mRNA and protein levels of c-Jun are increased in macrophages following pro- or anti-inflammatory stimulations. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment cluster analyses of microarray data using wild-type and c-Jun-deleted macrophages highlight the central function of c-Jun in macrophages, in particular for immune responses, IL production, and hypoxia pathways. Mice deficient for c-Jun in macrophages show an amelioration of inflammation and bone destruction in the serum-induced arthritis model. In vivo and in vitro gene profiling, together with chromatin immunoprecipitation analysis of macrophages, revealed direct activation of the proinflammatory factor cyclooxygenase-2 and indirect inhibition of the anti-inflammatory factor arginase-1 by c-Jun. Thus, c-Jun regulates the activation state of macrophages and promotes arthritis via differentially regulating cyclooxygenase-2 and arginase-1 levels.

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APA:

Hannemann, N., Jordan, J., Paul, S., Reid, S., Baenkler, H.-W., Sonnewald, S.,... Bozec, A. (2017). The AP-1 Transcription Factor c-Jun Promotes Arthritis by Regulating Cyclooxygenase-2 and Arginase-1 Expression in Macrophages. Journal of Immunology, 198(9), 3605-3614. https://dx.doi.org/10.4049/jimmunol.1601330

MLA:

Hannemann, Nicole, et al. "The AP-1 Transcription Factor c-Jun Promotes Arthritis by Regulating Cyclooxygenase-2 and Arginase-1 Expression in Macrophages." Journal of Immunology 198.9 (2017): 3605-3614.

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