ABSTRACT
In women, the association between chronic marijuana smoking and early miscarriage has long been known. Anandamide, a major endocannabinoid, mimics some of the psychotropic, hypnotic and analgesic effects of Delta(9)-tetrahydrocannabinol, the psychoactive component of marijuana. The uterus contains the highest concentrations of anandamide yet discovered in mammalian tissues and this suggests that it might play a role in reproduction. The production of small amounts of nitric oxide (NO) regulates various physiological events including implantation and myometrial relaxation, but in an inflammatory setting such as sepsis, NO has toxic effects as it is a free radical. The results presented in this study indicate that anandamide modulates NO production induced by lipopolysaccharide (LPS) in an in-vitro murine model. It was shown that LPS-induced NO synthesis and tissue damage were mediated by anandamide, as a cannabinoid receptor type I antagonist could block the effect of LPS (P < 0.001). This endotoxin inhibited anandamide uterine degradation (P < 0.05) and increased the expression of one of its synthesizing enzymes (P < 0.05). Contrary to the known anti-inflammatory and protective effects, in this model anandamide seems to act as a pro-inflammatory molecule modulating the production of NO induced by LPS. This proinflammatory effect of anandamide may be implicated in pathological reproductive events such as septic abortion.
Subject(s)
Arachidonic Acids/pharmacology , Lipopolysaccharides/pharmacology , Nitric Oxide/biosynthesis , Polyunsaturated Alkamides/pharmacology , Uterus/drug effects , Amidohydrolases/metabolism , Animals , Base Sequence , Blotting, Western , DNA Primers , Endocannabinoids , Female , Mice , Mice, Inbred BALB C , Polymerase Chain Reaction , Uterus/metabolismABSTRACT
Endocannabinoids are an important family of lipid-signaling molecules that are widely distributed in mammalian tissues and anandamide (AEA) was the first member identified. The uterus contains the highest concentrations of AEA yet discovered in mammalian tissues and this suggests that it might play a role in reproduction. Previous results from our laboratory have shown that AEA modulated NO synthesis in rat placenta. The production of small amounts of nitric oxide regulates various physiological reproductive processes such as implantation, decidualization and myometrial relaxation. But in an inflammatory setting such as sepsis, NO is produced in big amounts and has toxic effects as it is a free radical. The results presented in this study indicate that LPS-induced NO synthesis and tissue damage were mediated by AEA. Decidual LPS-induced NO production was abrogated either by co-incubation with CB1 (AM251) or CB2 (SR144528) antagonists which suggests that both receptors could be mediating this effect. On the other hand, LPS-induced tissue damage and this deleterious effect was partially abrogated by incubating tissue explants with LPS plus CB1 receptor antagonist. Our findings suggest that AEA, probably by increasing NO synthesis, participates in the deleterious effect of LPS in implantation sites. These effects could be involved in pathological reproductive events such as septic abortion.
Subject(s)
Arachidonic Acids/metabolism , Cannabinoid Receptor Modulators/metabolism , Decidua , Endocannabinoids , Lipopolysaccharides/pharmacology , Nitric Oxide/metabolism , Polyunsaturated Alkamides/metabolism , Abortion, Septic/immunology , Abortion, Septic/metabolism , Amidohydrolases/metabolism , Animals , Arachidonic Acids/pharmacology , Cannabinoid Receptor Antagonists , Cells, Cultured , Decidua/drug effects , Decidua/immunology , Decidua/metabolism , Female , Male , Mice , Mice, Inbred BALB C , Nitrates/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitrites/metabolism , Nitrogen/metabolism , Phospholipase D/metabolism , Pregnancy , Receptors, Cannabinoid/metabolismABSTRACT
Chiefly an intracellular parasite, Trypanosoma cruzi has a transient blood-borne stage (trypomastigote), the acute phase of Chagas' disease, during which surface trans-sialidase is expressed and shed by the parasite. It's immunosuppressive through the induction of apoptosis. Herein, we investigated the role of trans-sialidase as an immune modulator of allo- and xenoreactions. Trans-sialidase strongly inhibited human lymphocyte proliferation; a role for the interleukin-2 receptor CD25 was suggested by flow cytometry. These results may have implications both for the pathogenesis of Chagas' disease and for transplantation immunology.
