Interferon-γ stimulates human follicular dendritic cell-like cells to produce prostaglandins via the JAK-STAT pathway

초록

IFN-gamma plays a critical role in the regulation of innate and adaptive immunity. Paying attention to the emerging role of prostaglandins (PGs) as immune regulators, we attempted to establish the effect of IFN-gamma on PG production in human follicular dendritic cell-like HK cells and the underlying signaling pathway by using RNA interference technology. IFN-gamma induced COX-2 protein expression in HK cells in a time- and dose-dependent manner, which was not observed in peripheral blood monocytes. Although IFN-gamma induced phosphorylation of STAT1, STAT3, and STAT5, only STAT1 was essential for the COX-2 augmentation. The JAK kinases responsible for IFN-gamma-triggered STAT1 phosphorylation were JAK1 and JAK2, which were also required for the COX-2 induction. The essential requirement of JAK1 and JAK2 was verified by confocal microscopic analysis, since STAT1 phosphorylation and nuclear translocation were impaired in HK cells with these two kinases knocked down. Finally, we demonstrated that JAK1, JAK2, and STAT1 were indispensable for the actual enhancement of PG production in response to IFN-gamma stimulation. These results provide a novel insight into our understanding of IFN-gamma under inflammatory conditions and support the emerging concept of PGs as important immune regulators. (C) 2015 Elsevier Ltd. All rights reserved.

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