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

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Details zur Publikation

Autor(en): Hannemann N, Jordan J, Paul S, Reid S, Baenkler HW, Sonnewald S, Bäuerle T, Vera J, Schett G, Bozec A
Zeitschrift: Journal of Immunology
Jahr der Veröffentlichung: 2017
Band: 198
Heftnummer: 9
Seitenbereich: 3605-3614
ISSN: 0022-1767


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.



FAU-Autoren / FAU-Herausgeber

Baenkler, Hanns-Wolf Prof. Dr.
Medizinische Fakultät
Bäuerle, Tobias Prof. Dr.
Professur für Multimodale Bildgebung in der präklinischen Forschung
Bozec, Aline Prof. Dr.
Juniorprofessur für Osteoimmunologie
Hannemann, Nicole
Medizinische Fakultät
Reid, Stephen
Lehrstuhl für Biochemie
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III
Sonnewald, Sophia PD Dr.
Lehrstuhl für Biochemie
Vera González, Julio Prof. Dr.
Professur für Tumorimmunologie (Schwerpunkt Systembiologie)


Zitierweisen

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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Zuletzt aktualisiert 2018-07-10 um 02:37