EXPRESSION OF 3 FORMS OF MELANOMA GROWTH-STIMULATING ACTIVITY (MGSA) GRO IN HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS

Purpose. To characterize mRNA expression and protein production of the cytokine MGSA/gro in human retinal pigment epithelial (RPE) cells and to determine whether expression of MGSA/gro is modulated by serum and the cytokines interleukin 1beta (IL-1beta), tumor necrosis factoralph a (TNFalpha), or transforming growth factor beta (TGFbeta) mediators i mplicated in proliferative vitreoretinopathy (PVR). Methods. Reverse-t ranscription polymerase chain reaction was used to determine the stead y-state mRNA expression of three forms of MGSA/gro, alpha, beta, and g amma, by cultured human RPE cells in the presence or absence of recomb inant IL-1beta, TNFalpha, or TGFbeta, or when serum-starved cells were re-fed with medium containing serum. Immunocytochemistry was used to characterize RPE cell-associated MGSA/gro protein, and immunoprecipita tion of MGSA/gro from cell-conditioned medium was used to demonstrate MGSA/gro secretion. Results. MGSA/gro mRNA was expressed minimally und er basal conditions. Expression for all three forms of MGSA/gro mRNA w as induced in a dose- and time-dependent manner after exposure to IL-1 beta, to a lesser extent after exposure to TNFalpha, but not after exp osure to TGFbeta. Serum induced MGSA/gro alpha and gamma transcripts, but not beta transcripts. Cell-associated MGSA/gro was identified on R PE cells grown in the absence of cytokines, but MGSA/gro was not secre ted under these conditions. Exposure to IL-1beta did not consistently cause increased cell-associated MGSA/gro; however, IL-1beta induced se cretion of MGSA/gro in a time-dependent manner. Conclusion. MGSA/gro i s produced by human RPE in response to mediators implicated in PVR. Be cause MGSA/gro is a pleiotropic modulator of cell proliferation and in flammation, it may contribute to the intraocular wound healing respons e that characterizes PVR.