Chitosan oligosaccharides suppress LPS-induced IL-8 expression in human umbilical vein endothelial cells through blockade of p38 and Akt protein kinases

Abstract

Aim: To investigate whether and how COS inhibited IL-8 production in LPS-induced human umbilical vein endothelial cells (HUVECs). Methods: RT-PCR, enzyme-linked immunosorbent assays (ELISA) and Western blotting were used to study IL-8 expression and related signaling pathway. Wound healing migration assays and monocytic cell adhesion analysis were used to explore the chemotactic and adhesive activities of HUVECs. Results: COS 50-200 μg/mL exerted a significant inhibitory effect on LPS 100 ng/mL-induced IL-8 expression in HUVECs at both the transcriptional and translational levels. In addition, COS 50-200 μg/mL inhibited LPS-induced HUVEC migration and U937 monocyte adhesion to HUVECs in a concentration-dependent manner. Signal transduction studies suggest that COS blocked LPS-induced activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) as well as phosphorylation of p38 mitogen-activated protein kinase (MAPK) and phosphokinase Akt. Further, the over-expression of LPS-induced IL-8 mRNA in HUVECs was suppressed by a p38 MAPK inhibitor (SB203580, 25 μmol/L) or a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002, 50 μmol/L). Conclusion: COS inhibited LPS-induced IL-8 expression in HUVECs through the blockade of the p38 MAPK and PI3K/Akt signaling pathways.

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

“…3B. The charge of native ranibizumab was near neutral charge, at + 0.44 ± 1.5 mV and is in line with a previous study (22) . Particle zeta potential was predominantly positive as a result of the polycation, chitosan (58)(59)(60) .…”

Biochanin A inhibits lipopolysaccharide-induced inflammation in human umbilical vein endothelial cells

“…Vascular endothelial cells have been reported to play crucial roles in the development of vascular inflammation [3]. Stimulation of human vascular endothelial cells by LPS could induce NF-κB activation and cytokine TNF-α and IL-8 release and enhance expression of adhesion molecules including ICAM and VCAM [19,26]. Peroxisome proliferator-activated receptor gamma (PPAR-γ), belongs to the nuclear receptor superfamily, that plays important roles in glucose metabolism and energy homeostasis [11].…”

Chitosan oligosaccharides block LPS-induced O-GlcNAcylation of NF-κB and endothelial inflammatory response

“…It is also well recognized that LPS impair vascular endothelial function through aberrant inflammatory reactions (Bierhaus et al, 2000). Emerging evidence highlighted that LPS-induced vascular endothelial inflammatory response can be efficiently blocked by administration of chitosan oligosaccharides (COS) (Liu et al, 2011; Liu et al, 2010b).…”

“…Biological activities of COS have been extensively studied due to their high solubility (Da Silva et al, 2010; Kim & Rajapakse, 2005), absorption (Eijsink et al, 2010) and biocompatibility (Du et al, 2009). Increasingly emerging evidence indicate that COS exhibit anti-inflammatory activities in experimental models in vitro (Liu et al, 2011; Liu et al, 2010b) and in vivo (Qiao et al, 2011), in addition to those of antitumor (Fernandes et al, 2012), antifungal (Hussain et al, 2012), antimicrobial (Malcata et al, 2010; Tavaria et al, 2012), and free radical scavenging (Kim et al, 2012) activities. As such, COS have in recent years been recommended as healthy food supplements in Asian countries due to these properties (Nam et al, 2007; Nishimura et al, 1984).…”

“…Further in-depth studies with cultured cell models support the notion that the anti-inflammatory feature of COS may attribute to the suppression of NF-κB-dependent inflammatory gene expression. Indeed, pretreatments with COS significantly abolish the otherwise increased inflammatory cytokines by LPS, such as IL-1β (Pangestuti et al, 2011; Qiao et al, 2011), IL-6 (Liu et al, 2010b; Ma et al, 2011; Pangestuti et al, 2011; Yoon et al, 2007), IL-8 (Liu et al, 2011) and TNF-α (Ma et al, 2011; Pangestuti et al, 2011; Qiao et al, 2011; Yoon et al, 2007) in endothelial cells, as well as in macrophage and microglia. However, it has yet to be established how COS suppress NF-κB activation induced by LPS.…”