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Effect of TGF-beta on interferon-gamma-induced HLA-DR expression in human retinal pigment epithelial cells.
Invest Ophthalmol Vis Sci. 1994 Dec; 35(13):4253-9.IO

Abstract

PURPOSE

Retinal pigment epithelial (RPE) cells express human leukocyte antigen (HLA)-DR (class II) antigens when stimulated with interferon gamma (IFN-gamma) and may be capable of local antigen presentation. The authors examined the effect of transforming growth factor-beta (TGF-beta), a cytokine normally found in the eye, on the expression of these immunoregulatory molecules in vitro and attempted to determine the mechanism by which this cytokine acts.

METHODS

Human RPE cells were cultured in the presence of IFN-gamma and then stained immunohistochemically for HLA-DR antigens. TGF-beta 1 or TGF-beta 2 was added simultaneously with IFN-gamma or after 3 days of IFN-gamma treatment. In parallel experiments, RPE cells were pretreated with 4-phorbol-12 myristate-13 acetate (PMA), staurosporine, or calphostin C before stimulation with IFN-gamma or TGF-beta. Quantitative analysis was performed by fluorescence-activated cell sorting.

RESULTS

IFN-gamma induced HLA-DR expression on RPE cells. Both TGF-beta 1 and TGF-beta 2 were able to inhibit this effect. These inhibitory effects of TGF-beta were augmented by pretreatment with either PMA or calphostin C. Pretreatment of the cells with PMA before stimulation with IFN-gamma downregulated HLA-DR expression. Staurosporine pretreatment suppressed HLA-DR expression by IFN-gamma-stimulated RPE cells, but this was not additive with TGF-beta.

CONCLUSIONS

The authors conclude that TGF-beta 1 and TGF-beta 2 strongly inhibit the IFN-gamma-induced upregulation of class II antigens on human RPE cells. The modulation of these IFN-gamma and TGF-beta effects by calphostin C, staurosporine, and PMA treatment suggests involvement of the protein kinase C pathway.

Authors+Show Affiliations

Doheny Eye Institute, Los Angeles, CA 90033-4681.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8002245

Citation

Gabrielian, K, et al. "Effect of TGF-beta On Interferon-gamma-induced HLA-DR Expression in Human Retinal Pigment Epithelial Cells." Investigative Ophthalmology & Visual Science, vol. 35, no. 13, 1994, pp. 4253-9.
Gabrielian K, Osusky R, Sippy BD, et al. Effect of TGF-beta on interferon-gamma-induced HLA-DR expression in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 1994;35(13):4253-9.
Gabrielian, K., Osusky, R., Sippy, B. D., Ryan, S. J., & Hinton, D. R. (1994). Effect of TGF-beta on interferon-gamma-induced HLA-DR expression in human retinal pigment epithelial cells. Investigative Ophthalmology & Visual Science, 35(13), 4253-9.
Gabrielian K, et al. Effect of TGF-beta On Interferon-gamma-induced HLA-DR Expression in Human Retinal Pigment Epithelial Cells. Invest Ophthalmol Vis Sci. 1994;35(13):4253-9. PubMed PMID: 8002245.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of TGF-beta on interferon-gamma-induced HLA-DR expression in human retinal pigment epithelial cells. AU - Gabrielian,K, AU - Osusky,R, AU - Sippy,B D, AU - Ryan,S J, AU - Hinton,D R, PY - 1994/12/1/pubmed PY - 1994/12/1/medline PY - 1994/12/1/entrez SP - 4253 EP - 9 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 35 IS - 13 N2 - PURPOSE: Retinal pigment epithelial (RPE) cells express human leukocyte antigen (HLA)-DR (class II) antigens when stimulated with interferon gamma (IFN-gamma) and may be capable of local antigen presentation. The authors examined the effect of transforming growth factor-beta (TGF-beta), a cytokine normally found in the eye, on the expression of these immunoregulatory molecules in vitro and attempted to determine the mechanism by which this cytokine acts. METHODS: Human RPE cells were cultured in the presence of IFN-gamma and then stained immunohistochemically for HLA-DR antigens. TGF-beta 1 or TGF-beta 2 was added simultaneously with IFN-gamma or after 3 days of IFN-gamma treatment. In parallel experiments, RPE cells were pretreated with 4-phorbol-12 myristate-13 acetate (PMA), staurosporine, or calphostin C before stimulation with IFN-gamma or TGF-beta. Quantitative analysis was performed by fluorescence-activated cell sorting. RESULTS: IFN-gamma induced HLA-DR expression on RPE cells. Both TGF-beta 1 and TGF-beta 2 were able to inhibit this effect. These inhibitory effects of TGF-beta were augmented by pretreatment with either PMA or calphostin C. Pretreatment of the cells with PMA before stimulation with IFN-gamma downregulated HLA-DR expression. Staurosporine pretreatment suppressed HLA-DR expression by IFN-gamma-stimulated RPE cells, but this was not additive with TGF-beta. CONCLUSIONS: The authors conclude that TGF-beta 1 and TGF-beta 2 strongly inhibit the IFN-gamma-induced upregulation of class II antigens on human RPE cells. The modulation of these IFN-gamma and TGF-beta effects by calphostin C, staurosporine, and PMA treatment suggests involvement of the protein kinase C pathway. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/8002245/Effect_of_TGF_beta_on_interferon_gamma_induced_HLA_DR_expression_in_human_retinal_pigment_epithelial_cells_ L2 - https://iovs.arvojournals.org/article.aspx?volume=35&issue=13&page=4253 DB - PRIME DP - Unbound Medicine ER -