Smoke 2012 Scaricare Activator 32 Bits Italiano !FREE!

Nevertheless, investigation on the role played by CS in the gastrointestinal (GI) tract is limited. The experimental data available are often hardly comparable, mainly because of the different modalities of smoke exposure applied (active/passive smoking), the different smoke components studied [nicotine, carbon monoxide (CO), or whole cigarette], and the diverse administration methods used (oral, intraperitoneal, or subcutaneous). However, a region-specific modulation of the gut immune system has been reported after exposure to smoke. In the murine ileum, chronic smoke exposure caused an increase in apoptosis of the follicle-associated epithelium (Verschuere et al., 2012b; Allais et al., 2016; Allais et al., 2017), an increase in pro-inflammatory cytokines (Eliakim and Karmeli, 2003), and an excessive nitric oxide (NO) production (Allais et al., 2017). At variance with the ileum, the colon seems less sensitive to smoke irritants, as demonstrated by the failure of inflammatory cell recruitment in rats (Eliakim and Karmeli, 2003), the reduction of pro-inflammatory cytokines (Benson and Shepherd, 2011; Allais et al., 2017), and the changes in the CD4/CD8 ratio in mice (Daniluk et al., 2017).

In this background, the hormone relaxin (RLX) emerges as an interesting putative therapy to preventing intestinal alterations caused by exposure to smoke. In fact, the human relaxin-2 (RLX-2) or serelaxin (Hossain and Wade, 2014) has shown anti-inflammatory and anti-apoptotic properties in both in vitro and in vivo animal models (Samuel et al., 2007). Moreover, RLX-2 has been shown to be protective in a guinea pig model of chronic exposure to CS, limiting vascular damage, lung inflammation, and fibrosis (Pini et al., 2016a; Pini et al., 2016b). In the gut, in vitro exposure to porcine RLX and in vivo porcine RLX chronic treatment caused muscle relaxation due to a region-specific modulation of the expressions of different NO synthase isoforms (Baccari et al., 2007; Vannucchi et al., 2011; Baccari et al., 2012). No data are available on the effect of RLX in the gut exposed to smoking.

Chronic exposure to CS also caused changes in mucosal secretion. The capacity of CS to alter mucin production was reported in human lungs affected by chronic obstructive pulmonary disease (COPD) (Di et al., 2012; Kim, 2012) and in guinea pig airways (Pini et al., 2016b). The important role of mucins in maintaining intestinal homeostasis has been amply described (Snyder and Walker, 1987; Rhodes, 1997; Liu et al., 2020). Changes in the composition or quantity of mucins are common in inflammatory and neoplastic gut diseases (Rhodes, 1997; Shirazi et al., 2000; Al-Khayal et al., 2016; Allais et al., 2016), as well as in conditions of dysbiosis (alteration of the microbiota). Very few data are available on the effects of CS on mucin production in the gut. In mice exposed for 24 weeks to CS, Allais et al. (2016) showed an increase in the expression of mRNA encoding for secretory MUC2 and cell surface MUC3 in the ileum, as well as for cell surface MUC4 in the distal colon, without changes in the quantity and quality of goblet cells. At variance with these findings, we observed a significant shift toward an acidification of mucins in the ileum and a significant decrease in mucin content in the colon. The discrepancies between the results of Allais and coworkers and our results are likely related to differences in the time of CS exposition and the animal species used. However, the diverse patterns of mucin secretion following CS exposure in the two intestinal regions were in agreement with literature data (Allais et al., 2016; Allais et al., 2017). Presently, the shift toward more sulfated mucins in the ileum was interpretable as an attempt at defense against CS-mediated mucosal aggression. In fact, sulfation increased the anionic charge of mucus, making the carbohydrate side chains more resistant to bacterial enzymes and boosting the resistance of the epithelium to microbial invasion (Rhodes, 1997). In the colon, instead, the decrease in mucin content might have been dependent on the CS-induced dysbiosis. In fact, Allais et al. (2016; 2017), in the colon of mice chronically exposed to CS, reported the presence of dysbiosis characterized by an impairment in mucin-producing bacteria. Accordingly, in mice exposed for 10 weeks to CS, Zuo et al. (2014) reported the presence of inflammation in the ileum, but not in the colon, and attributed these different CS effects to the intrinsic properties of the two enteric regions; among these properties, the richness and variety in colonic microbiota might have played a main role (Zuo et al., 2014). Interestingly, a different sensitivity to CS was also reported in humans for recurrent IBD, i.e., CD and ulcerative colitis (UC). In fact, CS exacerbated the clinical course of CD, whereas ex-smokers affected by UC showed an increased frequency of disease relapse or worsening (Ananthakrishnan, 2013; Ananthakrishnan, 2015; Allais et al., 2017). 2b1af7f3a8

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Smoke 2012 Scaricare Activator 32 Bits Italiano !FREE!