Peroxisome proliferator-activated receptor-gamma activators inhibit IFN-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells
N. Marx et al., Peroxisome proliferator-activated receptor-gamma activators inhibit IFN-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells, J IMMUNOL, 164(12), 2000, pp. 6503-6508
Peroxisome proliferator-activated receptor-gamma (PPAR gamma), a member of
the nuclear hormone receptor superfamily originally shown to play an import
ant role in adipocyte differentiation and glucose homeostasis, is now known
to regulate inflammatory responses. Given the importance of endothelial ce
ll (EC)-derived chemokines in regulating leukocyte function and trafficking
, we studied the effects of PPAR gamma ligands on the expression of chemoki
nes induced in ECs by the Th1 cytokine IFN-gamma, Treatment of ECs with PPA
R gamma activators significantly inhibited IFN-gamma-induced mRNA and prote
in expression of the CXC chemokines IFN-inducible protein of 10 kDa (IP-10)
, monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell alpha-chemo
attractant (I-TAC), whereas expression of the CC chemokine monocyte chemoat
tractant protein-1 was not altered. PPAR gamma activators decreased IFN-ind
ucible protein of 10 kDa promoter activity and inhibited protein binding to
the two NF-kappa B sites but not to the IFN-stimulated response element IS
RE site. Furthermore, PPAR gamma ligands inhibited the release of chemotact
ic activity for CXC chemokine receptor 3 (CXCR3)-transfected lymphocytes fr
om IFN-gamma-stimulated ECs, These data suggest that anti-diabetic PPAR gam
ma activators might attenuate the recruitment of activated T cells at sites
of Th1-mediated inflammation.