Dipyrithione inhibits IFN-γ-induced JAK/STAT1 signaling pathway activation and IP-10/CXCL10 expression in RAW264.7 cells

This study investigates the effects of dipyrithione (PTS2) on the expression of IP-10/CXCL10, which has been observed in a wide variety of chronic inflammatory disorders and autoimmune conditions. RAW264.7 cells (a murine macrophage-like cell line) were cultured in the absence or in the presence of PTS2 (3-10 mu M) together with or without IFN-gamma (10 ng/ml). IP-10/CXCL10 expression was measured by specific enzyme-amplified immunoassays and reverse transcriptase-PCR (RT-PCR). Phosphorylation of JAK1, JAK2 and STAT1 were detected by Western blot analysis. We found that PTS2 inhibited IFN-gamma-induced up-regulation of IP-10/CXCL10 protein level in a dose- and time-dependent manner in RAW264.7 cells. RT-PCR experiments showed that PTS2 suppressed IFN-gamma-induced IP-10/CXCL10 expression at mRNA levels. Mechanistically, PTS2 prevented phosphorylation of JAK1, JAK2 and STAT1, but did not interfere with the p38 pathway. Furthermore, the inhibitory effect of PTS2 on IP-10/CXCL10 up-regulation was slightly stronger than JAK2 inhibitor AG490. PTS2 inhibits IFN-gamma-induced IP-10/CXCL10 expression in RAW264.7 cells by targeting the JAK/STAT1 signaling pathway, suggesting that PTS2 could exert anti-inflammatory effects through attenuating the formation of chemokine IP-10/CXCL10.