Prostaglandin E2 production by chronic graft-versus-host disease dermal fibroblasts

Abstract

Chronic graft versus host disease (cGVHD) across minor histocompatibility barriers is associated with the development of cutaneous fibrosis, disappearance of mast cells and immunosuppression. The idea, which has been the basis of our previous and present studies, is that fibroblasts are not only a target for modulation in cGVHD, but also have effector roles in this condition. In the present study we investigated the production of prostaglandin E2 (PGE2) and of collagen by cultured dermal fibroblasts obtained from cGVHD and control mice. Early in the development of the disease (Day 8) cGVHD fibroblasts generated constitutively more PGE2 (3-fold) than did control fibroblasts. Thereafter, PGE2 production declined to near normal levels by Day 20 post cGVHD induction. On the other hand, at this time point cGVHD fibroblasts displayed an enhanced synthesis of collagen as compared to the control fibroblasts and to earlier time points. Therefore, PGE2 synthesis appears to inversely correlate with collagen synthesis by cGVHD fibroblasts. We propose that fibroblasts may contribute to the development of immunosuppression, which characterizes the early phase of cGVHD.