Although it is known that prostaglandin (PG) F2α level is elevated in the plasma of patients with sepsis, the roles of PGF2α is still unknown. We aimed to clarify the roles of PGF2α in the regulation of lipopolysaccharide (LPS)-induced systemic inflammation. At 24 hours after LPS administration, neutrophil infiltration in peritoneal cavity, the mRNA expression of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and macrophage inflammatory protein-2, and tissue damages in lung, liver, and kidney were all increased. Inhibition of FP receptors significantly decreased LPS-induced neutrophil infiltration and lowered the mRNA expression of the pro-inflammatory cytokines. At 6 hour after LPS administration, the level of anti-inflammatory cytokine, IL-10 in peritoneal lavage fluid was higher than that in naïve mice. Inhibition of FP receptors in these mice increased IL-10 level further. Stimulation of isolated peritoneal neutrophils by LPS increased the gene expression of IL-10, which was further increased by AL8810 treatment. Administration of an anti-IL-10 antibody antagonized the AL8810-decreased mRNA expression of pro-inflammatory cytokines and tissue damages. These results indicate that inhibition of FP receptors by AL8810 attenuated LPS-induced systemic inflammation in mice via enhanced IL-10 production.
Keywords: FP receptor antagonist; neutrophil; prostaglandin F2α; systemic inflammation.
© 2020 Federation of American Societies for Experimental Biology.