Involvement of PKA signalling in anti‐inflammatory effects of chitosan oligosaccharides in IPEC‐J2 porcine epithelial cells

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Abrupt changes in dietary and environment lead to important morphological and functional adaptations in the gut of piglet at weaning, and weaning is also associated with upregulation of inflammatory cytokines in the intestine of piglet (Pie et al., 2004). Intestinal inflammation challenges the integrity of the mucosal barrier and disrupts epithelial barrier function (Bruewer et al., 2003; Leppkes, Roulis, Neurath, Kollias, & Becker, 2014). Controlling early intestinal inflammation is certainly a challenge in managing post‐weaning gut disorders in piglets (Pie et al., 2004). IPEC‐J2 cells, a cell line from jejunum epithelium isolated from a neonatal, unsuckled piglet (Berschneider, 1989), is an optimal model to study immune response in vitro. Previous studies have shown that inflammatory cytokines could be upregulated in IPEC‐J2 cells exposed to LPS (Arce, Ramirez‐Boo, Lucena, & Garrido, 2010), pathogenic bacteria (Geens & Niewold, 2010) and virus (Liu, Li, Wen, et al., 2010).
TNF‐α, one of the major inflammatory cytokines, can induce intracellular signalling cascades by interaction with its receptors expressed on different cells to mediate systemic inflammation and immune response (Leppkes et al., 2014; Nizamutdinova et al., 2007). TNF‐α‐induced overexpression and oversecretion of related pro‐inflammatory have been illustrated in intestinal epithelium cells before (Kim et al., 2005; Yousef, Pichyangkura, Soodvilai, Chatsudthipong, & Muanprasat, 2012). Furthermore, TNF‐α is able to influence tight junction expression in intestinal epithelium cells, but the results are not consistent (Leppkes et al., 2014; Ma et al., 2004; Poritz, Harris, Kelly, & Koltun, 2011).
Chitosan are deacetylated products of chitin, which occur as the major structural component in the exoskeleton of crab and shrimp shells and the cell of fungi and yeast (Azuma, Ifuku, Osaki, Okamoto, & Minami, 2014). Chitosan oligosaccharides (COS), the oligosaccharide of glucosamine in β‐1, 4‐glucosidic bond linkage, are degraded products of chitosan or the deacetylated and degraded products of chitin by chemical and enzymatic hydrolysis (Liu, Li, Huang, et al., 2010). COS have a better solubility and low viscosity compared with chitin and chitosan due to shorter chain lengths and are easily absorbed through the intestine, and quickly get into the blood flow to exert a systemic biological effects in the organism (Kim & Rajapakse, 2005). Previous records have manifested that COS, as feed additives, have positive effects on growth performance, digestibility and intestinal morphology in pigs (Swiatkiewicz, Swiatkiewicz, Arczewska‐Wlosek, & Jozefiak, 2015). In addition, COS possess various biological activities such as antimicrobial activity (Jeon, Park, & Kim, 2001), antitumour activity (Shen, Chen, Chan, Jeng, & Wang, 2009), immunomodulatory (Feng, Zhao, & Yu, 2004), anti‐inflammation activity (Yousef et al., 2012), antioxidant activity (Ngo, Kim, & Kim, 2008) and promotion of fracture healing (Jung, Moon, & Kim, 2006). Interestingly, anti‐inflammatory activity of COS is related to their molecular weight and degree of deacetylation (Lee, Senevirathne, Ahn, Kim, & Je, 2009; Pangestuti, Bak, & Kim, 2011; Yang et al., 2010). Yousef et al. (2012) suggested that high‐molecular‐weight COS (5,000~10,000 Da) have anti‐inflammatory activity in enterocyte. Furthermore, Ma et al. (2011) suggested that anti‐inflammatory activity of COS is regulated by mitogen‐activated protein kinases (MAPKs) and phosphatidylinositol 3‐kinase (PI3K)/Akt pathways.
However, data are still scarce about the protective effect of low‐molecular‐weight COS (LCOS) with high degree of deacetylation against inflammation in enterocyte. In addition, previous works have neglected cAMP/PKA pathway, which is involved in regulating many physiological and pathophysiological process. The purpose of this study was to determine whether LCOS could inhibit inflammation induced by TNF‐α in IPEC‐J2 cells, as well as their underlying mechanisms.
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