Long-term exposure to prostaglandin E2 enhances LPS-induced production of inflammatory cytokines by monocytes

GONZALES PRIN, M; SABATTE, JUAN; CEBALLOS, ANA; REMES LENICOV, FEDERICO; ODDI, J; GEFFNER, JORGE; VARESE, AUGUSTO; FÉRNANDEZ, N

Mar del Plata

Congreso; SAIC SAI SAFE 2016; 2016

SAI

Prostaglandin E2 (PGE2) is a pleiotropic agent produced during acute and chronic 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.Monocytes were purified from peripheral blood mononuclear cells by gradient centrifugation. TNFalpha production was evaluated by ELISA and intracytoplasmic staining followed by flow cytometry, while IL-1beta, IL-6 and IL-10 were measured by ELISA. phenotype was analyzed by flow cytometry.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 TNFalpha, IL-1beta and IL-6 was analyzed. We found that long-term exposure to PGE2 results in a marked increase in the production of all inflammatory cytokines analyzed: 75 +/- 8 vs 56 +/- 7% of TNFalpha positive cells (n=9), 2115 +/- 615 vs 251 +/- 49 pg/ml for IL-1beta (n=4), and 6950 +/- 145 vs 3069 +/- 110 pg/ml for IL-6 (n=4), for monocytes incubated in the presence vs absence of PGE2, respectively (p