Chitosan inhibits prostaglandin E2 formation and cyclooxygenase-2 induction in lipopolysaccharide-treated RAW 264.7 macrophages.
Chitosan, a deacetylated chitin, has been reported to accelerate the wound healing and exert anti-inflammatory effect but the possible mechanisms involved are still unclear. Enhanced production of prostaglandin E2 (PGE2) and pro-inflammatory cytokines has been shown to contribute to immunosuppression and cytotoxicity during wound healing. In this study, we examined the effect of chitosan on cyclooxygenase pathway and cytokines production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results first demonstrated that chitosans (MW=50,000, 150,000 or 300,000) significantly inhibit the overproduction of PGE2 as well as cyclooxygenase-2 (COX-2) protein expression and activity accompanied by attenuation of pro-inflammatory cytokines production such as tumor necrosis factor-alpha and interleukin-1beta formation but increase of the anti-inflammatory cytokine, IL-10, formation in LPS-treated RAW 264.7 macrophages. These results suggest that the beneficial effect of chitosan on wound healing may be associated, at least partly, with the inhibition of PGE2 production by suppressing COX-2 induction and activity as well as attenuation of pro-inflammatory/anti-inflammatory cytokines ratio in activated macrophages.
Chou
Tz-Chong
TC
Department of Physiology and Biophysics, National Defense Medical Center, Taiwan, ROC. tcchou@ms5.hinet.net
Fu
Earl
E
Shen
E-Chin
EC
D000818:Animals; D002460:Cell Line; D002686:Chitin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D048271:Chitosan; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D007527:Isoenzymes; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002686:Chitin; D048271:Chitosan; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone