Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1 induced by LPS in endothelial cells by inhibiting MAP kinase signaling

Abstract

Abstract. The expression of adhesion molecules in endothelial cells elicited by lipopolysaccharide (LPS) is involved in the adhesive interaction between endothelial cells and monocytes in inflammation. In this study, in order to characterize the anti-inflammatory effects of chitosan oligosaccharides (COS) on LPS-induced inflammation and to elucidate the underlying mechanisms, the mRNA levels of E-selectin and intercellular adhesion molecule-1 (ICAM-1) were measured in porcine iliac artery endothelial cells (PIECs). When these cells were treated with COS, the LPS-induced mRNA expression of E-selectin and ICAM-1 was reduced through the inhibition of the signal transduction cascade, p38 mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB). Moreover, through the inhibition of p38 MAPK and ERK1/2, COS suppressed the LPS-induced NF-κB p65 translocation. We found that COS suppressed the phosphorylation of p38 MAPK and the translocation of NF-κB p65 into the nucleus in a dose-dependent manner, and inhibited the adhesion of U973 cells to PIECs. Based on these results, it can be concluded that COS downregulate the expression of E-selectin and ICAM-1 by inhibiting the phosphorylation of MAPKs and the activation of NF-κB in LPS-treated PIECs. Our study demonstrates the valuable anti-inflammatory properties of COS. IntroductionChitosan oligosaccharides (COS), consisting of D-glucosamine linked via β-1,4-glycosides, are derived from chitosan by chemical or enzymatic hydrolysis (1). It has been reported that COS exhibit various biological activities, such as antitumor (2) and antioxidant properties (3), owing to their low molecular weight, high absorption, solubility and biocompatibility (4). In addition, recent studies have paid more attention to the regulatory role of COS in inflammatory responses (5,6).Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, can act as an endotoxin and initiates serious inflammatory responses in vitro and in vivo (7,8) by upregulating the expression of adhesion molecules and cytokines, such as E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and tumor necrosis factor-α (TNF-α) (9,10). Endothelial cells are the target of inflammatory responses and thereby, of a number of severe disorders, including sepsis and multiple organ dysfunctions that occur via LPS stimulation (11). In this study, we detected the expression of the adhesion molecules, E-selectin and ICAM-1 in LPS-treated porcine iliac artery endothelial cells (PIECs), since the upregulation of adhesion molecules and the increased secretion of cytokines and chemokines are known to occur during endothelial cell activation (12)(13)(14).The evolutionary conserved family of mitogen-activated protein kinases (MAPKs) includes extracellular p38 MAPK, extracellular regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) (15). Numerous environmental stresses, such as osmotic shock, ...

Chitosan Oligosaccharides Attenuate Ocular Inflammation in Rats with Experimental Autoimmune Anterior Uveitis

“…In this study, we showed that the protein level of ICAM-1 in the ICB was upregulated and that COS significantly decreased the ICAM-1 expression in a dose-dependent manner. Our findings are consistent with a previous report by Li et al, who demonstrated that COS downregulated the expression of ICAM-1 by inhibiting the activation of NF- κ B in LPS-treated porcine iliac artery endothelial cells [43]. …”

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

“…In this study, LCOS also inhibited the mRNA expression of NF-κB. Previous study has shown that COS suppressed the translocation of NF-κB p65 into the nucleus in a dosedependent manner (Li, Xu et al, 2014). In addition, COS inhibit NF-κB binding activity and the expression of RELA and IKBKB genes of NF-κB induced by TNF-α; moreover, COS show stimulatory effects on AP-1-binding activity and JUN gene of AP-1 pathway in Caco-2 cells (Bahar, O'Doherty, Maher, McMorrow, & Sweeney, 2012).…”

The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

“…Adhesion molecules are involved in the adhesive interaction between endothelial cells and monocytes in inflammation. COS down regulate the expression of adhesion molecules E-selectin and ICAM-1 by inhibiting the phosphorylation of MAPKs and the activation of NF-κB in LPS-treated porcine iliac artery endothelial cells [ 70 ]. Sulfated chitosan inhibits P-selectin-mediated HL-60 leukocyte adhesion.…”