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

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-kappa B (NF-kappa B). Moreover, through the inhibition of p38 MAPK and ERK1/2, COS suppressed the LPS-induced NF-kappa B p65 translocation. We found that COS suppressed the phosphorylation of p38 MAPK and the translocation of NF-kappa B 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-kappa B in LPS-treated PIECs. Our study demonstrates the valuable anti-inflammatory properties of COS.

脂多糖（LPS）诱导的内皮细胞黏附分子表达参与炎症过程中内皮细胞与单核细胞之间的黏附相互作用。在本研究中，为了表征壳寡糖（COS）对LPS诱导的炎症的抗炎作用并阐明其潜在机制，我们测量了猪髂动脉内皮细胞（PIECs）中E -选择素和细胞间黏附分子 - 1（ICAM - 1）的mRNA水平。当这些细胞用COS处理时，通过抑制信号转导级联p38丝裂原活化蛋白激酶（MAPK）/细胞外调节蛋白激酶1/2（ERK1/2）和核因子 - κB（NF - κB），LPS诱导的E -选择素和ICAM - 1的mRNA表达降低。此外，通过抑制p38 MAPK和ERK1/2，COS抑制了LPS诱导的NF - κB p65易位。我们发现COS以剂量依赖的方式抑制p38 MAPK的磷酸化以及NF - κB p65向细胞核的易位，并抑制U973细胞与PIECs的黏附。基于这些结果，可以得出结论：在LPS处理的PIECs中，COS通过抑制MAPKs的磷酸化和NF - κB的激活而下调E -选择素和ICAM - 1的表达。我们的研究证明了COS具有有价值的抗炎特性。