1,25(OH)(2)D-3 and cAMP synergistically induce complement 5a receptor messenger RNA

Complement 5a receptor (C5aR) mediates both acute and chronic participation of monocytes in the immune response. In the human U937 monoblast, C5aR is maximally expressed 4 days after treatment with 1,25(OH)(2)D-3 (or cycloheximide) and prostaglandin E(2) combined, The authors asked whether these agents altered expression of C5aR messenger RNA (mRNA). Unstimulated U937 cells expressed neither C5aR mRNA nor C5a binding. Complement 5aR mRNA rose 3 hours after prostaglandin E(2) application and fell to basal levels by 12 hours. This early rise in C5aR mRNA did not cause an acute rise in C5a binding, which gradually increased between 1 and 4 days, Neither 1,25(OH)(2)D-3 nor cycloheximide induced expression of C5aR mRNA in the absence of prostaglandin E(2) but did enhance prostaglandin E(2)-stimulated C5aR mRNA expression and C5a binding, The authors observed a late increase in C5aR mRNA at day 3 in treated cells. Inhibition of this late rise in mRNA with 5,6-dichlorobenzimidazole riboside attenuated C5a binding by 65%, indicating its importance in the generation of C5a binding sites. The expression of functional C5aR is, therefore, a complex process involving regulation at transcriptional and posttranscriptional levels.