Open Access

REVIEW

Opposite roles of STAT and PPARγ in the induction of p21^WAF1 expression by IL-13 in human peripheral blood monocytes

Marc Dubourdeau^1,2, Gérald Chêne¹, Agnès Coste¹, José Bernad¹, Jean-Claude Lepert¹, Claudine Orfila¹, Bernard Pipy¹, Denis Rousseau³

1 Macrophages, médiateurs de l’inflammation et interactions cellulaires UPRES EA 2405 - INSERM IFR 31, CHU Rangueil, Toulouse, France
2 Ambiotis, Incubateur Midi-Pyrénées, 29 rue Jeanne Marvig, 31400 Toulouse, France
3 CEA, DSV, iRTSV, Laboratoire de biochimie et biophysique des systèmes intégrés, 38054 Grenoble, and Université Joseph Fourier, Grenoble, France

* Corresponding Author: D. Rousseau,

European Cytokine Network 2008, 19(4), 156-165. https://doi.org/10.1684/ecn.2008.0134

Accepted 15 September 2008;

Abstract

The cyclin kinase inhibitor p21^WAF1 is expressed in most, if not all, differentiated cells in the human body and represents an important regulator of cell cycle control and terminal differentiation in the monocyte/macrophage lineage. It has been reported in macrophage cell lines that p21^WAF1 expression is sensi-tive to numerous molecules including cytokines, but nothing was known about p21^WAF1 regulation in human peripheral blood monocytes in response to Th2 cytokines. We report here, that IL-13 increases p21^WAF1 expres-sion in human blood monocytes. This induction is a transcription-dependent event, leading to an increase in mRNA content. We show that the signalling pathway for IL-13-induced p21^WAF1 expression may involve the IL-4R alpha and the IL-13R alpha1 chains, and the tyrosine and JAK2 kinases. Also, p21^WAF1 plasmid-based gene activation only requires a minimal p21^WAF1 promoter, containing a putative PPRE. Since IL-13 signalisa-tion involves PPARγ, we tested PPARγ involvement in p21^WAF1 gene activation by using metabolic inhibitors of arachidonic acid metabolism, or by restoring PPARγ expression in a defective cell line. We found that inhibition of PPARγ increases IL-13-induced p21^WAF1 gene expression in these models. These data argue that IL-13 upre-gulates p21^WAF1 expression in monocytes via JAK/STAT pathway, and that the activation of PPARγ by this cytokine can counteract this induction.

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