Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell

Guilds in the transition to modernity: the cases of Germany, United Kingdom, and the Netherlands

One important aspect of the transition to modernity is the survival of elements of the Old Regime beyond the French Revolution. It has been claimed that this can explain why in the late 19th and early 20th centuries some Western countries adopted national corporatist structures while others transformed into liberal market economies. One of those elements is the persistence or absence of guild traditions. This is usually analyzed in a national context. This paper aims to contribute to the debate by investigating the development of separate trades in Germany, the United Kingdom and the Netherlands throughout the 19th century. We distinguish six scenarios of what might have happened to crafts and investigate how the prevalence of each of these scenarios in the three countries impacted on the emerging national political economies. By focusing on trades, rather than on the national political economy, our analysis demonstrates that in each country the formation of national political economies and citizenship rights was not the result of a national pattern of guild survival. Rather, the pattern that emerged by the end of the 19th century was determined by the balance between old and new industries, and between national and regional or local government

Vagus nerve activity augments intestinal macrophage phagocytosis via nicotinic acetylcholine receptor alpha4beta2.

BACKGROUND and AIMS: The vagus nerve negatively regulates macrophage cytokine production via the release of acetylcholine (ACh) and activation of nicotinic acetylcholine receptors (nAChR). In various models of intestinal inflammation, vagus nerve efferent stimulation ameliorates disease. Given the actively constrained cytokine responses of intestinal macrophages, we explored the effect of nAChR activation on endocytosis and phagocytosis by macrophages residing in the peritoneal and mucosal compartment. METHODS: The phagocytic uptake by intestinal and peritoneal macrophages was measured by fluorescence-activated cell sorter analysis, and the nAChR involved was determined by pharmacologic blockade, short hairpin RNA-assisted gene knockdown, and the use of specific nAChR knockout mice. The effect of electrical vagus nerve stimulation on epithelial translocation and macrophage uptake of luminal particles was studied in mice. RESULTS: In isolated intestinal and peritoneal macrophages, nAChR activation enhanced endocytosis and phagocytosis. This effect was mediated via stimulated recruitment of GTPase Dynamin-2 to the forming phagocytic cup. These effects involve nAChR alpha4/beta2, rather than nAChR alpha7. Despite enhanced bacterial uptake, acetylcholine reduced NF-kappaB activation and pro-inflammatory cytokine production, while stimulating anti-inflammatory interleukin-10 production. Vagus nerve stimulation in mice altered mucosal immune responses by augmenting epithelial transport and uptake of luminal bacteria by lamina propria macrophages. CONCLUSIONS: ACh enhances phagocytic potential while inhibiting immune reactivity via nAChR alpha4/beta2 in mouse macrophages. Hence, vagus nerve efferent activity may stimulate surveillance in the intestinal mucosa and peritoneal compartment