@Article{ecn.2008.0134,
AUTHOR = {Marc Dubourdeau, Gérald Chêne, Agnès Coste, José Bernad, Jean-Claude Lepert, Claudine Orfila, Bernard Pipy, Denis Rousseau},
TITLE = {Opposite roles of STAT and PPARγ in the induction of p21<sup>WAF1</sup> expression by IL-13 in human peripheral blood monocytes},
JOURNAL = {European Cytokine Network},
VOLUME = {19},
YEAR = {2008},
NUMBER = {4},
PAGES = {156--165},
URL = {http://www.techscience.com/ECN/v19n4/65917},
ISSN = {1952-4005},
ABSTRACT = {The cyclin kinase inhibitor p21<sup>WAF1</sup>
 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<sup>WAF1</sup> expression is sensi-tive
to numerous molecules including cytokines, but nothing was known about p21<sup>WAF1</sup> regulation in human
peripheral blood monocytes in response to Th2 cytokines. We report here, that IL-13 increases p21<sup>WAF1</sup> 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<sup>WAF1</sup> expression may involve the
IL-4R alpha and the IL-13R alpha1 chains, and the tyrosine and JAK2 kinases. Also, p21<sup>WAF1</sup> plasmid-based
gene activation only requires a minimal p21<sup>WAF1</sup> promoter, containing a putative PPRE. Since IL-13 signalisa-tion
involves PPARγ, we tested PPARγ involvement in p21<sup>WAF1</sup> 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<sup>WAF1</sup> gene expression in these models. These data argue that IL-13 upre-gulates
p21<sup>WAF1</sup>
 expression in monocytes via JAK/STAT pathway, and that the activation of PPARγ by this
cytokine can counteract this induction.},
DOI = {10.1684/ecn.2008.0134}
}