Human RPE cells infected with toxoplasma gondii cpregllate mRNA express on and secretion of IL-6, GM-CSF, IL-1 and ICAM-1

Purpose: We have recently dcmonstrated Toxcplasma gondii (T. gondii) replication in human RPE cells (HRPE) and the nihi )ition o! this replication hv the cvlokine IFN gamma These studies suggest that T. gendii replication within HRPE cells may serve as a useful model to evaluate the factors that regulate retinal inteclion. Since HRPE cells produce cytokmes which inf ucnce infectious and inflammatory diseases, the present study was initiated to investigate the cytokme production by /' cumin infected HRPH cells. Methods: HRPE cultures were inoculated with /'. Kondu. RH strain. At various times post-inocula ion, culture supernatents were collected and ihe levels of cytokines were determined by ELISA. Cytokme mRNA expression was analyzed by RT-PCR and Northern blot tnalyses. Results: T. gondii infection of HRPE cells resulted in a significant increise in the secretion of the following cytokines: IL-6 (con 95 vs.T. gondii 2100 pg/ml). GM-CSF (con 31 vs/T. gondii 207 pg/ml), IL-1 (con 1 vs.T. gondii 11 pg/ml). In contrast, T. gundii infection of HRPE cells did not increase the secretion of TNF alpha. IL-4. IL-10. IL-12 or IL-15 These data indicate that HRPE ce 1 is not activated to produce cytokines which directly participate in modulating Thl and Th2 responses. Moreover, 7'. %onciii infections induced the secretic n of the adhesion moieculc, ICAM- U con H vs.7. fftmüii 35 ng/mi) by these cells. Njrthcrn blot and RT-PCR analysis indicated upregulationof IL-6. ICAM-1, GM-CSF and IL-1 mRNA in HRPF infected with T. gondii. Conclusions: HRPE secrele IL-6, GM-CSF. IL-1 and ICAM-1 b> Ihe activation of their gene expression in response to T.gondii infection. Secretion of these cytokines and adhesion molecules by HRPE may play a critical role in the pathogenesis of T. gondii infection.