Inhibition of the transcription factors AP-1 and NF-kappa B in CD4 T cellsby peroxisome proliferator-activated receptor gamma ligands

Citation
P. Wang et al., Inhibition of the transcription factors AP-1 and NF-kappa B in CD4 T cellsby peroxisome proliferator-activated receptor gamma ligands, INT IMMUNO, 1(4), 2001, pp. 803-812
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INTERNATIONAL IMMUNOPHARMACOLOGY
ISSN journal
1567-5769 → ACNP
Volume
1
Issue
4
Year of publication
2001
Pages
803 - 812
Database
ISI
SICI code
1567-5769(200104)1:4<803:IOTTFA>2.0.ZU;2-U
Abstract
The peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the nuclear hormone receptor superfamily, is essential for adipocyte di fferentiation and glucose homeostasis. PPAR gamma has been found recently t o regulate macrophage activation in response to mitogens and inflammation. Our study shows PPAR gamma to be preferentially expressed in the nuclei of resting T cells and to increase upon activation of T cells by either anti-C D3 and anti-CD28 or phorbol myristyl acetate (PMA). We also found the PPAR gamma ligand ciglitizone to attenuate the activation of T cells by inhibiti ng cytokine gene expression and anti-CD3 and anti-CD28 or PMA-induced proli ferative responses. Inhibition of both the proliferative response and infla mmatory cytokine expression in CD4 T cells was correlated with suppression of the activated transcription factors AP1 and NF-kappaB. PPAR gamma ligand s also strongly inhibited SEA-induced V beta3 T cell activation in vivo. Th ese results, together with previous findings of the inhibitory effect of PP AR gamma ligands on activated macrophages. provide clear evidence for PPAR gamma as a negative regulator of the inflammatory activation of both macrop hage and T cells. PPAR gamma may thus be a potential therapeutic target for the treatment of autoimmunity. (C) 2001 Elsevier Science B.V. All rights r eserved.