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Prolonged IL-1&#x03B2; exposure alters neurotransmitter and electrically induced Ca<sup>2+</sup> responses in the myenteric plexus Export

Neurogastroenterology & Motility, Vol. 9999, No. 9999. (2009)

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HEIRS Inflammatory Bowel Disease, Colititis, and IBS's tags for this article

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Background Infection and inflammatory diseases of the gut results in profound changes of intestinal motor function. Acute administration of the pro-inflammatory cytokine interleukin-103B2 (IL-103B2) was shown to have excitatory and neuromodulatory roles in the myenteric plexus. Here we aimed to study the effect of prolonged IL-103B2 incubation on the response of myenteric neurones to different stimuli.Methods  Longitudinal muscle myenteric plexus preparations (LMMP's) of the guinea pig jejunum were incubated for 24 h in medium with or without IL-103B2. After loading with Fluo-4, calcium imaging was used to visualize activation of neurones. The response to application of serotonin (5-HT), substance P (SP) and ATP or to electrical fibre tract stimulation (eFTS) was tested. Expression of nNOS, HuD, calbindin and calretinin was compared by immunohistochemistry.Key Results  IL-103B2 concentration-dependently influenced the neuronal responsiveness and duration of the [Ca2+]i rises to 5-HT and ATP, while it also affected the Ca2+-transient amplitudes induced by 5-HT, ATP and SP. Ca2+-transients in response to eFTS were observed in significantly more neurones per ganglion after IL-103B2 (10221210 and 10221211 mol L22121). Peak [Ca2+]i rise after eFTS was concentration-dependently decreased by IL-103B2. The duration of the [Ca2+]i rise after eFTS was prolonged after IL-103B2 10221212 mol L22121. IL-103B2 (1022129 mol L22121) incubation did not affect the number of nNOS, calretinin and calbindin expressing neurones, nor did it induce neuronal loss (HuD).Conclusions & Inferences  In this study, IL-103B2 differentially modulates the neuronal response to eFTS and neurotransmitter application in the myenteric plexus of guinea pigs. This cytokine could be implicated in the motility disturbances observed during gastrointestinal inflammation.


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