Cytokine modulation of costimulatory molecules on human fetal retinal pigment epithelial cells.
OBJECTIVE
Experiments were performed to evaluate the effect of various pro- and anti-inflammatory cytokines on the human fetal retinal pigment epithelium's (HFRPE) expression of major histocompatibility complex (MHC) and costimulatory molecules.


METHODS
Pure cultures of HFRPE cells were isolated. HFRPE cells were incubated in the presence of Interferon-gamma (IFN-gamma), IFN-beta, Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-1beta (IL-1beta), Tumor Growth Factor-beta (TGF-beta), and a combination of IFN-gamma and TGF-beta (pre-incubation and simultaneously incubated). The expression of MHC class I and class II, Intercellular cell adhesion molecule (ICAM-1), B7-1 (CD80), and B7-2 (CD86) molecules was quantitatively analyzed by flow cytometry.


RESULTS
The cultured HFRPE cells expressed high levels of MHC class I and low levels of MHC class II and ICAM-1 molecules. After culture with the above mentioned cytokines, IFN-gamma up-regulated the HFRPE's expression of MHC class II and ICAM-1. IFN-beta and IL-beta1 only up-regulated the expression of ICAM-1. TGF-beta was unable to suppress the up-regulatory effect of IFN-gamma in HFRPE cells (pre-incubated and simultaneously incubated). The other cytokines did not have any significant effect on HFRPE's expression of MHC I and II or the selected costimulatory molecules.


CONCLUSIONS
Our findings indicate that TGF-beta cannot suppress up-regulating effects of IFNgamma- on HFRPE's expression of MHC and costimulatory molecules. Overall, the weak or lack of expression of costimulatory molecules after stimulation with various cytokines further confirms that HFRPE cells are weak antigen presenting cells.
Farrokh-Siar
L
L
Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA. lfarrokh@midway.uchicago.edu
Rezai
K A
KA
Palmer
E M
EM
Patel
S C
SC
Ernest
T J
TJ
van Seventer
G A
GA
D000938:Antigen-Presenting Cells / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005333:Fetus; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
D015703:Antigens, CD; D000954:Antigens, Surface; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1