Crosstalk between interleukin-6 and corticotropin-releasing factor modulate submucosal plexus activity and colonic secretion

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• 作者：Dervla O&rsquo ; Malley^a ; ^b ; ^{d.omalley@ucc.ie} ; John F. Cryan^a ; ^c ; Timothy G. Dinan^a ; ^d
• 关键词：CRF ; corticotropin releasing factor ; CRFR ; CRF receptor ; CRD ; colo-rectal distension ; GI ; gastrointestinal ; HPA ; hypothalamic-pituitary-adrenal ; IBS ; irritable bowel syndrome ; IL ; interleukin ; IL-6R ; interleukin-6 receptor ; ISC ; short circuit current ; JAK
• 刊名：Brain, Behavior, and Immunity
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：30
• 期：Complete
• 页码：115-124
• 全文大小：1029 K

文摘

Background

Irritable bowel syndrome (IBS) is a common disorder of the gut with symptoms such as diarrhoea, constipation, abdominal pain and bloating, that are frequently exacerbated by stress. Circulating levels of the pro-inflammatory cytokine, interleukin-6 (IL-6), which can activate colonic enteric neurons, are elevated in IBS patients. These studies aim to explore the relationship between IL-6 and the stress peptide, corticotropin-releasing factor (CRF) in colonic submucosal neurons.

Methods

Calcium imaging, Ussing chamber electrophysiology and immunohistochemistry were conducted on rat distal colons to investigate potential crosstalk between IL-6 and CRF.

Key results

Colonic secretions from the maternal separation rat model of IBS stimulated increases in intracellular calcium in na?ve submucosal neurons via CRF1 receptors (n = 15, p < 0.05). Moreover, IL-6 (n = 50, p < 0.01) but not IL-1¦Â (n = 46, p > 0.05) or TNF¦Á (n = 46, p > 0.05) potentiated the CRF-evoked calcium response. CRF (1 ¦ÌM, 1 h, n = 5) stimulation also induced colonic secretion of IL-6 and inhibited the pro-secretory effects of IL-6 on colonic ion transfer (n = 12).

Conclusions and inferences

These studies demonstrate the modulatory effects of CRF on colonic IL-6 secretion, neuronal activation and secretory function. These findings may provide an insight into the molecular mechanisms underlying symptom flares in IBS during periods of high stress.