Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, P.R. China.
Int J Mol Med. 2014 Feb;33(2):392-400. doi: 10.3892/ijmm.2013.1589. Epub 2013 Dec 13.
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.
脂多糖 (LPS) 诱导的内皮细胞黏附分子的表达参与了炎症中内皮细胞与单核细胞之间的黏附相互作用。在这项研究中,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,测量了猪髂动脉内皮细胞 (PIEC) 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 丝裂原激活蛋白激酶 (MAPK)/细胞外调节蛋白激酶 1/2 (ERK1/2) 和核因子-κB (NF-κB),抑制了 LPS 诱导的 E-选择素和 ICAM-1 的 mRNA 表达。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 的磷酸化和 NF-κB p65 向核内的易位,并抑制了 U973 细胞与 PIECs 的黏附。基于这些结果,可以得出结论,COS 通过抑制 MAPKs 的磷酸化和 LPS 处理的 PIECs 中 NF-κB 的激活,下调了 E-选择素和 ICAM-1 的表达。我们的研究表明 COS 具有有价值的抗炎特性。