TGF-beta increases leukotriene C-4 synthase expression in the monocyte-like cell line, THP-1

The goal of this study was to determine whether cytokines modulate leukotri ene C-4 (LTC4) synthase expression in mononuclear phagocytes. A panel of cy tokines was surveyed for changes in LTC4 synthase mRNA in THP-1 cells. TGF- beta 1, -2, and -3 had significant stimulatory effects. The addition of TGF -beta resulted in a time-dependent increase in LTC4 synthase mRNA at 6 h, w hich persisted through 48 h, Furthermore, this conditioning resulted in an increase in immunoreactive protein for LTC4 synthase through 7 days. TGF-be ta conditioning of cells resulted in a time- and dose-dependent increase in stimulated LTC4 synthase activity. Following transient transfection of THP -1 cells with a promoter-reporter construct containing 1.2 kb of the LTC4 s ynthase promoter, TGF-beta treatment resulted in a 2-fold increase in repor ter activity. Conditioning with TGF-beta did not prolong the half-life of L TC4 synthase mRNA, as assessed by RNase protection assays in actinomycin D- treated cells. Cycloheximide exposure experiments revealed that new protein synthesis was not required for the observed stimulatory effect of TGF-beta on LTC4 synthase mRNA, We conclude that LTC4 synthase expression is increa sed at a transcriptional level by TGF-beta in mononuclear phagocytes.