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


METHODS
RAW264.7 cells (a murine macrophage-like cell line) were cultured in the absence or in the presence of PTS2 (3-10 microM) 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.


RESULTS
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.


CONCLUSIONS
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.
Han
Cui
C
Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210046, People's Republic of China.
Fu
Jin
J
Liu
Ziwen
Z
Huang
Huang
H
Luo
Lan
L
Yin
Zhimin
Z
D000818:Animals; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000276:immunology*; D004789:Enzyme Activation; D007371:Interferon-gamma / Q000276:immunology*; D053613:Janus Kinase 1 / Q000276:immunology*; D053614:Janus Kinase 2 / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D054357:Chemokine CXCL10; D011725:Pyridines; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007371:Interferon-gamma; C032196:dipyrithione; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D048051:p38 Mitogen-Activated Protein Kinases