INFLAMMATORY CYTOKINES INDUCE INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) MESSENGER-RNA SYNTHESIS AND PROTEIN SECRETION BY HUMAN RETINAL-PIGMENT EPITHELIAL-CELL CULTURES
Cn. Nagineni et al., INFLAMMATORY CYTOKINES INDUCE INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) MESSENGER-RNA SYNTHESIS AND PROTEIN SECRETION BY HUMAN RETINAL-PIGMENT EPITHELIAL-CELL CULTURES, Cytokine, 8(8), 1996, pp. 622-630
Retinal inflammatory diseases in man are associated with an upregulati
on in the expression of intercellular adhesion molecule-1 (ICAM-1) in
cells within the retina and with an increase in soluble ICAM-1 within
the vitreous, These studies suggest that this protein may contribute t
o immunopathological processes within the eye, The effects of inflamma
tory mediators on the regulation of the expression and secretion of IC
AM-1 by human retinal pigment epithelial cell cultures (HRPE) were inv
estigated in order to identity the possible source of soluble ICAM-1 a
nd the conditions which enhance its production, Immunofluorescence stu
dies on TNF-alpha and/or IFN-gamma treated HRPE cells demonstrated cel
lular expression of ICAM-1 which was predominantly localized to interc
ellular junctions, Moreover, treatment of HRPE for 24 h with tumour ne
crosis factor alpha (TNF-alpha) (10 ng/ml), interferon gamma (IFN-gamm
a) (500 u/ml), interleukin 1 alpha (IL-1 alpha) (10 ng/ml) and IL-1 be
ta (10 ng/ml) results in the secretion of ICAM-1, ranging from 9 to 13
ng per 10(6) cells, IFN-gamma acts synergistically with (TNF-alpha) a
nd IL-1 in the secretion of ICAM-1 by HRPE. Only 1.75 ng of soluble IC
AM-1 was detected in untreated HRPE cells, In contrast, lipopolysaccha
ride (LPS), IL-6, IFN-alpha or TGF-beta did not exhibit any influence
on ICAM-1 secretion by these cells, Northern blot analysis reveals an
increased expression of ICAM-1 mRNA in HRPE stimulated with IFN-gamma,
TNF-alpha or IL-1 for 24 h, In untreated cells, ICAM-1 mRNA is not de
tectable, There is a progressive increase in ICAM-1 mRNA levels in cyt
okine-treated HRPE, that reaches steady state by 12 h, Furthermore, a
close correlation is noted between ICAM-1 mRNA levels and the secretio
n of ICAM-1 protein, suggesting regulation at the level of gene transc
ription, ICAM-1 secretion by RPE might actively participate in the imm
une reactions in the retina, by recruiting and activating lymphocytes,
and contribute to the immunopathological processes in inflammatory di
seases. (C) 1996 Academic Press Limited