Inhibition of the transcription factors AP-1 and NF-κB in CD4 T cells by peroxisome proliferator-activated receptor γ ligands

The peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the nuclear hormone receptor superfamily, is essential for adipocyte differentiation and glucose homeostasis. PPAR gamma has been found recently to 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-CD3 and anti-CD28 or phorbol myristyl acetate (PMA). We also found the PPAR gamma ligand ciglitizone to attenuate the activation of T cells by inhibiting cytokine gene expression and anti-CD3 and anti-CD28 or PMA-induced proliferative responses. Inhibition of both the proliferative response and inflammatory cytokine expression in CD4 T cells was correlated with suppression of the activated transcription factors AP1 and NF-kappaB. PPAR gamma ligands also strongly inhibited SEA-induced V beta3 T cell activation in vivo. These results, together with previous findings of the inhibitory effect of PPAR gamma ligands on activated macrophages. provide clear evidence for PPAR gamma as a negative regulator of the inflammatory activation of both macrophage 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 reserved.