Effects of endotoxin and macrophage-related cytokines on the contractile activity of the gravid murine uterus.
Immune cell trafficking and activity are implicated in the parturition process, but little is known about the role of macrophages in control of uterine contractility at term. In the present study, we tested the hypothesis that endotoxin (lipopolysaccharide [LPS]) enhances uterine contractile activity through a mechanism that involves activation of resident macrophages. Various uterotonins and anti-inflammatory mediators were added to a standard muscle bath preparation that contained strips of uterus from Day 15 pregnant C3H/HeN mice. Spontaneous and agonist-induced contractile activity was enhanced following LPS treatment. LPS increased amplitude but not frequency of contractions. Addition of anti-inflammatory cytokines, interleukin 10 or transforming growth factor beta, to suppress macrophage activation did not block LPS-induced increases in contractility. By contrast, indomethacin given to block prostaglandin production suppressed the LPS-induced increase in amplitude of contractions. These findings suggest that an inflammatory response, possibly mediated by activation of macrophages and prostaglandins, participates in the regulation of amplitude but not frequency of contractile activity by the murine uterus before onset of parturition.
Mackler
Ari M
AM
Center for Perinatal Biology, Department of Physiology, Loma Linda University School of Medicine, Loma Linda, California 92350, USA.
Ducsay
Travis C
TC
Ducsay
Charles A
CA
Yellon
Steven M
SM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D010121:Oxytocin; D007213:Indomethacin