Opposing roles of TGF-1β in prostaglandin production by human follicular dendritic cell-like cells

초록

Prostaglandins (PGs) are recognized as important immune regulators. Using human follicular dendritic cell (FDC)-like HK cells, we have investigated the immunoregulatory role of PGs and their production mechanisms. The present study was aimed at determining the role of TGF-beta in IL-1 beta-induced cyclooxygenase-2 (COX-2) expression by immunoblotting. COX -2 is the key enzyme responsible for PG production in HK cells. TGF-beta, when added simultaneously with IL-1 beta, gave rise to an additive effect on COX-2 expression in a dose-dependent manner. However, TGF-beta inhibited IL-1 beta-stimulated COX-2 expression when it was added at least 12 h before IL-1 beta addition. The inhibitory effect of TGF-beta was specific to IL-1 beta-induced COX-2 expression in HK cells. The stimulating and inhibitory effects of TGF-beta were reproduced in IL-1 beta-stimulated PG production. Based on our previous results of the essential requirement of ERK and p38 MAPK5 in TGF-beta-induced COX-2 expression, we examined whether the differential activation of these MAPK5 would underlie the opposing activities of TGF-beta. The phosphorylation of ERK and p38 MAPKs was indeed enhanced or suppressed by the simultaneous treatment or pre-treatment, respectively. These results suggest that TGF-beta exerts opposing effects on IL-beta-induced COX -2 expression in HK cells by differentially regulating activation of ERK and p38 MAPKs. (C) 2016 Elsevier Ltd. All rights reserved.

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