Nicotine inhibits cytokine synthesis by mouse colonic mucosa

Dijk, J. P. M. Van; Madretsma, G. S.; Keuskamp, Zosca J.; Zijlstra, Freek J.

doi:10.1016/0014-2999(95)00211-3

Cited by 60 publications

(24 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…61 Nicotine also inhibits the ex vivo production of IL-2 and TNF␣ by mononuclear cells isolated from healthy volunteers 57 and reduces the production of IL-1␤ and TNF␣ by healthy mouse colonic mucosa. 58 It has also been reported to reduce the circulating concentrations of IL-2 and IL-6 in male Sprague-Dawley rats. 59 Studies of UC patients also suggest smoking and/or nicotine has an ameliorative effect on cytokine production.…”

Section: Possible Therapeutic Roles Of Nicotine In Uc Nicotine Decreamentioning

confidence: 98%

See 1 more Smart Citation

Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis

McGilligan

Wallace

Heavey

et al. 2007

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

Ulcerative colitis (UC) is characterized by impairment of the epithelial barrier and the formation of ulcer-type lesions, which result in local leaks and generalized alterations of mucosal tight junctions. Ultimately, this results in increased basal permeability. Although disruption of the epithelial barrier in the gut is a hallmark of inflammatory bowel disease and intestinal infections, it remains unclear whether barrier breakdown is an initiating event of UC or rather a consequence of an underlying inflammation, evidenced by increased production of proinflammatory cytokines. UC is less common in smokers, suggesting that the nicotine in cigarettes may ameliorate disease severity. The mechanism behind this therapeutic effect is still not fully understood, and indeed it remains unclear if nicotine is the true protective agent in cigarettes. Nicotine is metabolized in the body into a variety of metabolites and can also be degraded to form various breakdown products. It is possible these metabolites or degradation products may be the true protective or curative agents. A greater understanding of the pharmacodynamics and kinetics of nicotine in relation to the immune system and enhanced knowledge of gut permeability defects in UC are required to establish the exact protective nature of nicotine and its metabolites in UC. This review suggests possible hypotheses for the protective mechanism of nicotine in UC, highlighting the relationship between gut permeability and inflammation, and indicates where in the pathogenesis of the disease nicotine may mediate its effect.

show abstract

Section: Possible Therapeutic Roles Of Nicotine In Uc Nicotine Decreamentioning

confidence: 98%

“…[57][58][59][60][61][62] Because smoking seems to be protective in UC, why it has the opposite effect in CD must be addressed. 1t is possible that smoking decreases gut permeability in UC by acting against the inflammatory response underlying this increased permeability.…”

Section: Smoking and Differences In Permeability Between Uc And CDmentioning

confidence: 99%

Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis

McGilligan

Wallace

Heavey

et al. 2007

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

show abstract

“…However, increased availability of ACh to bind to nicotinic receptors may represent a braking strategy to counter the prosecretory effects of the cholinergic muscarinic system that would contribute to diarrhea. Should the findings in the DSS model system extrapolate to human colonic inflammation, then nicotinic receptormediated NO regulation of epithelial ion transport represents another facet of the putative therapeutic action of nicotine, along with nicotine-NO-mediated muscle relaxation (14), direct immunosuppression (45), and stimulation of mucin synthesis (11).…”

Section: Fluorescence Micrographs Of Inos and Glial Fibrillatory Acmentioning

confidence: 99%

Dextran sodium sulfate-induced colitis reveals nicotinic modulation of ion transport via iNOS-derived NO

Green¹,

Ho²,

Sharkey³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

. Dextran sodium sulfate-induced colitis reveals nicotinic modulation of ion transport via iNOS-derived NO. Am J Physiol Gastrointest Liver Physiol 287: G706 -G714, 2004. First published April 15, 2004 10.1152/ajpgi.00076.2004.-In normal colon, ACh elicits a luminally directed Cl Ϫ efflux from enterocytes via activation of muscarinic receptors. In contrast, in the murine model of dextran sodium sulfate (DSS)-induced colitis, an inhibitory cholinergic ion transport event due to nicotinic receptor activation has been identified. The absence of nicotinic receptors on enteric epithelia and the ability of nitric oxide (NO) to modulate ion transport led us to hypothesize that NO mediated the cholinergic nicotinic receptor-induced changes in ion transport. Midportions of colon from control and DSS-treated mice were examined for inducible NO synthase (iNOS) expression by RT-PCR and immunofluorescence or mounted in Ussing chambers for assessment of cholinergic-evoked changes in ion transport (i.e., shortcircuit current) with or without pretreatment with pharmacological inhibitors of NO production. iNOS mRNA and protein levels were increased throughout the tissue from DSS-treated mice and, notably, in the myenteric plexus, where the majority of iNOS immunoreactivity colocalized with the enteric glial cell marker glial fibrillary acidic protein. The drop in short-circuit current evoked by the cholinomimetic carbachol in tissue from DSS-treated mice was prevented by selective inhibitors of iNOS activity {N 6 -(1-iminoethyl)-lysine HCl and N- [3-(aminomethyl)benzyl]acetamidine} or an NO scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide] or by removal of the myenteric plexus. Thus, in this model of colitis, a "switch" occurs from muscarinic to nicotinic receptor-dominated control of cholinergic ion transport. The data indicate a novel pathway involving activation of nicotinic receptors on myenteric neurons, resulting in release of NO from neurons or enteric glia and, ultimately, a dampening of stimulated epithelial Cl Ϫ secretion that would reduce secretory diarrhea.short-circuit current; chloride; inflammatory bowel disease WATER MOVEMENT between the gut lumen and the interstitium is critically important for hydrating the surface of the enteric epithelium, providing the medium for contact digestion and nutrient absorption, and reducing the contact of pathogens and potentially noxious bacterial or environmental toxins with the enterocytes. This key function of the epithelium is accomplished by the coordinated activity of ion channels, cotransporters, and energy-dependent ion pumps that are asymmetrically arranged in the cell membrane of the polarized epithelium: this allows for vectorial ion transport, creating the driving forces for directed water movements (2). Many intrinsic and extrinsic agents influence epithelial ion transport, including neurotransmitters (e.g., ACh), biogenic amines, nu-

show abstract

“…In mouse models of IBD, nicotine had differential effects on the small and large bowel, 29,30 with increased jejunal inflammation and decreased colonic inflammation together with inhibition of proinflammatory cytokines. 31 An inhibitory effect of nicotine was shown on IL10 in peripheral blood 32 without any effect on IL2 and TNF␣, whereas others suggested that nicotine reduced TNF␣ release from monocytic cells. 33 In this study we investigated the effects of nicotine on peripheral blood mononuclear cell (PBMC) responses from IBD patients and healthy controls (HCs).…”

mentioning

confidence: 97%

Does nicotine influence cytokine profile and subsequent cell cycling/apoptotic responses in inflammatory bowel disease?

Aldhous

Prescott

Roberts

et al. 2008

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

show abstract

Nicotine inhibits cytokine synthesis by mouse colonic mucosa

Cited by 60 publications

References 8 publications

Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis

Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis

Dextran sodium sulfate-induced colitis reveals nicotinic modulation of ion transport via iNOS-derived NO

Does nicotine influence cytokine profile and subsequent cell cycling/apoptotic responses in inflammatory bowel disease?

Contact Info

Product

Resources

About