Attenuation of IFN-γ-induced B7-H1 expression by 15-deoxy-delta(12,14)-prostaglandin J2 via downregulation of the Jak/STAT/IRF-1 signaling pathway.

B7-H1, which belongs to the B7 family of costimulatory molecules, is implicated in the ability of tumors to evade the host immune response. The development of evasion mechanisms within the tumor microenvironment may be responsible for poor therapeutic responses. In this manuscript, we report that the 15-deoxy-δ(12,14)-prostaglandin J2 (15d-PGJ2), peroxisome proliferator-activated receptor gamma (PPARγ) activator leads to the downregulation of the cancer-associated expression of B7-H1 in response to interferon-gamma (IFN-γ) and the associated signaling cascades. The expression of B7-H1 from IFN-γ-induced B16F10 melanoma cells was measured with flow cytometric analysis. The regulatory mechanisms of 15d-PGJ2 on cellular signaling pathways were examined using Western blot and electrophoretic mobility shift assays. The flow cytometric analysis revealed that the B7-H1 costimulatory molecule is significantly upregulated in B16F10 melanoma cells by stimulation with IFN-γ. However, 15d-PGJ2 strongly downregulates B7-H1 expression in IFN-γ-stimulated B16F10 melanoma cells. Furthermore, the significant damping effect of 15d-PGJ2 on B7-H1 expression involves the inhibition of the tyrosine phosphorylation of Janus kinase (Jak) and signal transducer(s) and activator(s) of transcription (STAT) and, thereby, the interferon regulatory factor-1 (IRF-1) trans-activation of STAT. These effects of 15d-PGJ2 were not abrogated by the PPARγ antagonist GW9662, indicating that they occur through a PPARγ-independent mechanism. In this study, we demonstrate that 15d-PGJ2 suppresses the IFN-γ-elicited expression of B7-H1 by the inhibition of IRF-1 transcription via the Jak/STAT signaling pathway through a PPARγ-independent mechanism in mouse melanoma cells.

Seo SK ，Seo DI ，Park WS ，Jung WK ，Lee DS ，Park SG ，Choi JS ，Kang MS ，Choi YH ，Choi I ，Yu BC ，Choi IW ... -  《-》

Inhibition of IL-10-induced STAT3 activation by 15-deoxy-Delta12,14-prostaglandin J2.

Ji JD ，Kim HJ ，Rho YH ，Choi SJ ，Lee YH ，Cheon HJ ，Sohn J ，Song GG ... -  《RHEUMATOLOGY》

15-deoxy-Delta12,14-prostaglandin J2 inhibits INF-gamma-induced JAK/STAT1 signalling pathway activation and IP-10/CXCL10 expression in mesangial cells.

Panzer U ，Zahner G ，Wienberg U ，Steinmetz OM ，Peters A ，Turner JE ，Paust HJ ，Wolf G ，Stahl RA ，Schneider A ... -  《-》

15-deoxy-Delta12,14 prostaglandin J2 up-regulates Kruppel-like factor 4 expression independently of peroxisome proliferator-activated receptor gamma by activating the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signal tra

Chen ZY ，Tseng CC 《MOLECULAR PHARMACOLOGY》

15-Deoxy-12,14-prostaglandin J2 inhibits interferon gamma induced MHC class II but not class I expression on ARPE cells through a PPAR gamma independent mechanism.

Willermain F ，Dulku S ，Gonzalez NS ，Blero D ，Driessens G ，De Graef C ，Caspers L ，Bruyns C ... -  《PROSTAGLANDINS & OTHER LIPID MEDIATORS》