Involvement of eicosanoids and macrophage-like cells in cytokine-mediated changes in rat myenteric nerves |
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Authors: | Anne Rühl Irene Berezin Stephen M Collins |
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Institution: | Intestinal Disease Research Program, McMaster University Medical Centre, Hamilton, Ontario, Canada |
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Abstract: | Proinflammatory cytokines alter function in enteric nerves, but little is known about underlying mechanisms. This study was designed to investigate the roles of prostanoids and of macrophage-like cells in cytokine-induced suppression of 3H]norepinephrine release from rat myenteric plexus. The release of 3H from jejunal longitudinal muscle-myenteric plexus preparations that had been loaded with 3H]norepinephrine was measured. Measurements of 3H release as well as concentrations of prostaglandin E2 and leukotriene were made in preparations exposed to interleukin 1β plus interleukin 6 and in the presence or absence of piroxicam, 5-lipoxygenase inhibitor MK886, cycloheximide, or cyclosporin A. An ultrastructural analysis was also performed to investigate the presence of macrophage-like cells in the myenteric plexus. Interleukin 1β plus interleukin 6 suppressed 3H release and caused an increase in tissue prostaglandin E2 butnot leukotriene E4. Piroxicam and cycloheximide but not MK886 attenuated the cytokine-induced increase in prostaglandin E2 and the suppression of 3H]norepinephrine release. Ultrastructural analysis showed macrophage-like cells in the plexus, and the cytokine effects were inhibited by cyclosporin A. Prostanoids but not leukotrienes mediate the cytokine-induced suppression of norepinephrine release, and the results of this study suggest that macrophage-like cells are also involved. |
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Keywords: | Abbreviations: CsA |
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