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
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.