Effect of interferon-gamma on the expression of transforming growth factor-beta by human corneal fibroblasts: role in corneal immunoseclusion.
Human corneal fibroblasts (HCF) inhibit T cell alloresponse in mixed leukocyte response-human corneal fibroblast coculture. The inhibition is contact independent, insensitive to indomethacin, and is enhanced by pretreatment of HCF with interferon-gamma (IFN-gamma). To investigate cytokine-dependent mechanisms of inhibition of T cell alloresponse by HCF, the capacity of cultured HCF to produce transforming growth factor-beta (TGF-beta) and the modulatory role of IFN-gamma on their TGF-beta production were investigated by radioreceptor binding inhibition assay (RRA) and the standard mink cell bioassay (BIA). The net total TGF-beta concentration of 4 day culture supernatants from IFN-gamma-treated HCF, measured by RRA, was 11.5 ng/ml. The net total bioactive TGF-beta concentrations of 4 day culture supernatants from HCF, before and after treatment with IFN-gamma, measured by BIA, were 2.0 and 4.8 ng/ml, respectively. These findings indicate that HCF produce TGF-beta and increase their TGF-beta output under the influence of the proinflammatory cytokine IFN-gamma. Media-borne TGF-beta binding proteins appeared to be primarily responsible for the discrepancy between the TGF-beta values measured by RRA and BIA. Active exclusion of TGF-beta binding proteins from intraocular fluids may have an important role in the maintenance of TGF-beta-dependent ocular immune privilege. Corneal fibroblasts may utilize TGF-beta-dependent mechanisms to maintain the immunosecluded environment of the cornea and to preserve the homeostasis of corneal optical competency. Interferon-gamma may enhance corneal immunoseclusion by upregulating the TGF-beta output of the corneal fibroblasts.
Abrahamian
A
A
Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Xi
M S
MS
Donnelly
J J
JJ
Rockey
J H
JH
D001681:Biological Assay; D002460:Cell Line; D003315:Cornea / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007518:Isoantibodies / Q000096:biosynthesis*; D011869:Radioligand Assay; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D007518:Isoantibodies; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma