Paradoxical effect of prostaglandin E2 on the inflammatory profile of human monocytes

F. REMES LENICOV; M. GONZALEZ PRINZ; A. VARESE; J. GEFFNER; A. CEBALLOS

Buenos Aires

Congreso; Reunion Anual SAI; 2015

Sociedad Argentina de Inmunología

Background: Prostaglandin E2 (PGE2) is a pleiotropic agent produced during inflammation. It mediates either inflammatory or anti-inflammatory effects on different cells and experimental systems. It is well known that activation of monocytes by LPS results in the production of inflammatory cytokines and that the presence of PGE2 during LPS-stimulation results in the inhibition of this response. Here, we analyzed whether long-term exposure of monocytes to PGE2 also resulted in the inhibition of their proinflammatory profile.Methods: Monocytes were purified from peripheral blood mononuclear cells by conventional procedures. TNF-α production was evaluated by intracytoplasmic staining and flow cytometry, while IL-1β and IL-6 were measured by ELISA. Phenotype was analyzed by flow cytometry.Results. Monocytes were preincubated for 15 hs with PGE2 (10-8M), and then stimulated by LPS (25 ng/ml). After 24 hs of culture, the production of TNF-α, IL-1β and IL-6 was analyzed. We found that long-term exposure to PGE2 results in a marked increase in the production of all cytokines analyzed: 75 ± 8 vs 56 ± 7% of TNF-α + cells (n=9), 2115 ± 615 vs 251 ± 49 pg/ml for IL-1β (n=4), and 6950 ± 145 vs 3059 ± 110 pg/ml for IL-6 (n=4), for monocytes incubated in the presence vs absence of PGE2, respectively (p<0.05). No differences in the expression of TLR4 and HLA-DR were found between monocytes treated, or not, with PGE2.Conculsions: We found that long-term exposure of human monocytes to PGE2 results in an increas