Anti-ICAM1 monoclonal antibody, clone 7H23

In recent years, various studies have demonstrated a role for endogenously derived specialized proresolving mediators such as resolvins in the resolution of inflammation. In exploring the signaling mechanisms, in the present study we show that Resolvin D1 (RvD1) reduces LPS-induced endothelial cell (EC)-monocyte interactions via blocking H2O2-mediated PP2A inactivation, NF kappa B activation and ICAM1 and VCAM1 expression. In addition, we found that H2O2-mediated SHP2 inhibition leads to tyrosine phosphorylation and inactivation of PP2A by LPS, which in turn, accounts for increased NF kappa B activation and ICAM1 and VCAM1 expression facilitating EC-monocyte interactions and all these LPS-mediated responses were reduced by RvD1. Furthermore, the suppression of NF kappa B activation, ICAM1 and VCAM1 expression and EC and monocyte interactions by RvD1 involved its receptors ALX/FPR2 and GPR32 as inhibition or neutralization of these receptors negated its effects. Besides, pertussis toxin completely prevented the effects of RvD1 on inhibition of LPS-induced H2O2 production, SHP2 and PP2A inactivation, NF kappa B activation, ICAM1 and VCAM1 expression and EC and monocyte interactions. Together, these observations suggest that RvD1 via activation of Gi-coupled ALX/FPR2 and GPR32 receptors blocks LPS-induced H2O2-mediated SHP2 and PP2A inactivation, NF kappa B activation, ICAM1 and VCAM1 expression and EC-monocyte interactions, which could be one of the several possible mechanisms underlying the anti-inflammatory actions of this specialized proresolving mediator.

The present study tested a hypothesis that dietary fish oil (eicosapentaenoic acid + docosahexaenoic acid) in a commonly achievable dose ameliorates a systemic inflammation in pigs. Two groups of pigs of 16 animals each were fed a diet with either 2.5% of fish oil (F) or a control diet with 2.5% of palm oil (P). After 70 days of fattening, eight F and eight P pigs were challenged (F+; P+) i.v. by lipopolysaccharide. After 3 h, all pigs were sacrificed and blood, liver and visceral adipose tissue (VAT) samples were taken. No significant effect (P>0.05) of dietary oil on the feed intake and daily weight gain was found out. Less neutrophils (16.8% v. 28.8%; P0.05) between F+ and P+ pigs in the peroxisome proliferator-activated receptor gamma, GPR120, Adipor1 and Adipor2 (adiponectin receptor) gene expression, respectively, was established; plasma adiponectin was the same (21.1 ng/ml) in F+ and P+ pigs. In comparison with the P+ pigs, increased expression of the lipopolysaccharide-binding protein (LBP) gene and intercellular adhesion molecule 1 (ICAM1) gene was found out in the liver of the F+ pigs; expression of the tumor necrosis factor alpha (TNF alpha) gene was higher in the liver but lower in the VAT of the F+ pigs (P<0.05). The F+ pigs had higher (P<0.05) plasma concentration of both anti-inflammatory cytokine interleukin-4 (0.46 v. 0.04 ng/ml) and pro-inflammatory TNF-alpha (13.41 v. 7.72 ng/ml). It was concluded that dietary fish oil at the tested amount had a negligible effect on expression of the evaluated receptor genes and plasma adiponectin, and had an ambiguous effect on expression of cytokine genes and plasma cytokine levels.