Antiflammin-2 prevents HL-60 adhesion to endothelial cells and prostanoid production induced by lipopolysaccharides.
We studied the effect of antiflammin-2 (AF-2) on adhesion molecule expression by HL-60 cells and endothelial (ECV304) cells stimulated by lipopolysaccharides (LPSs), and on leukocyte-endothelial cell interaction in an in vitro coculture system. The action of AF-2 on prostanoid production in these experimental conditions was also tested. LPS increased the adhesion molecule expression, such as lymphocyte function-associated antigen-1 and membrane attack complex-1 on HL-60 cells and E-selectin and intercellular adhesion molecule-1 on ECV304 cells. The LPS-stimulated adhesion molecule expression on HL-60/ECV304 coculture system was higher than on HL-60 or ECV304 cultures. LPS also induced HL-60 adhesion to ECV304 monolayer and thromboxane B(2) and prostaglandin E(2) (PGE(2)) production in HL-60 culture and PGE(2) in ECV304 culture. Prostanoid production by HL-60/ECV304 cocultures was higher than by simple cultures. AF-2 inhibited the enhancement of adhesion molecule expression induced by LPSs, especially E-selectin. Thus, AF-2 significantly reduced the HL-60 adhesion to endothelial cells stimulated by LPSs. AF-2 also inhibited prostanoid synthesis by ECV304 cells or HL-60/ECV304 coculture challenged by LPSs. In conclusion, AF-2 reduced HL-60 adhesion to endothelial cells, suggesting that it reduces inflammation by blocking leukocyte trafficking and the subsequent eicosanoid production.
Moreno
J J
JJ
Department of Physiology, Faculty of Pharmacy, Barcelona University, Barcelona, Spain. moreno@farmacia.far.ub.es
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; D008070:Lipopolysaccharides; D009842:Oligopeptides; D010446:Peptide Fragments; C064647:antiflammin P2; D013929:Thromboxane B2; D015232:Dinoprostone