Cyclooxygenase 2 production

FIGURE 6.3 Chemical structures of some lipoxygenase and cyclooxygenase-2 products of AEA and 2-AG, of prostamides and their synthetic analog, bimatoprost, and of prostaglandin glyceryl esters. 

Inhibition of inflammatory cytokines (Fig. 2) Humanized monoclonal anti-TNF antibodies (Infliximab (Remicade ), Adalimumab (Humira )) bind with high selectivity to human TNF-a and neutralize its activity. Thereby, infliximab decreases the effects of enhanced TNF levels during inflammatory disease such as production of proteases, chemokines, adhesion molecules, cyclooxygenase products (prostaglandins), and proinflammatory molecules such as interleukin-1 and -6. The antibodies may also recognize membrane-bound TNF-a on lymphocytes and other immune cells. These cells may subsequently become apoptotic or are eliminated via Fc-receptor-mediated phagocytosis. 

Table I. Cells in Which Arachidonic Acid Metabolism Is Stimulated by Palytoxin to Produce Cyclooxygenase Products ...

Inflammatory cell phenomenon are also contributors to lipid peroxidation. Activated neutrophils may adhere to damaged endothelium and amplify traumatic, ischaemic or ischaemia-reperfiision injury. Many cyclooxygenase products of the metabolism of atachidonic acid modulate the inflammatory responses of cells. Macrophages, neutrophils and microglia are important sources of reactive oxygen at the injury site. When activated, they produce a respiratory burst that is traced to activated nicotinamide adenine dinucleotide (NADPH/NADH) oxidase. 

Ellis, E.F., Wright, K.F., Wei, E.P. and Kontos, H.A. (1981) Cyclooxygenase products of arachidonic acid metabolism in cat cerebral cortex after experimental concussive brain injury, J. Neurochem. 37, 892-896. 

Lundberg C, Marceau F, Hugli TE (1987) C5a-induced hemodynamic and hematologic changes in the rabbit The role of cyclooxygenase products and polymorphonuclear leukocytes. Am J Pathol 128 471-483. 

It was concluded that 1) bradykinin has a biphasic effect on afferent arterioles 2) both dilation and constriction may be mediated by bradykinin B2 receptors and 3) the mechanisms of vasodilation and vasoconsbiction are due to cyclooxygenase products, not nitric oxide. 

Among these six flavonoids, licochalcones A and B inhibited formation of cyclooxygenase products HETT and TXB2, and the 12-lipoxygenase product 12-HETE dose-dependently "Fig. (39)". 

A more recent clinical evaluation found that even this potent inhibition still permitted AA-induced aggregation, which could be prevented by coadministration of small aspirin doses. This apparently prevented cyclooxygenase product accumulation capable of platelet aggregation in spite of TXA2 absence. Dazoxiben may become the forerunner of this new type of antithrombotic. 

The roots of Saposhnikovia divaricata ("Bou-hu" in Japan and "Fang-Feng" in China) have been traditionally used as an antiphlogistic, an antipyretic and an analgesic in China and Japan. We isolated three polyacetylene compounds, i.e., falcarindiol, panaxynol and (8E)-heptadeca-l,8-dien-4,6-diyn-3,10-diol "Fig. (32)", from Saposhnikoviae Radix. As shown in "Fig. (33)", these polyacetylene compounds inhibited the formation of cyclooxygenase products HHT and TXB2dose-dependently in human platelets. 

Stadler, J., Harbrecht, B. G., DiSilvio, M., Curran, R. D., Jordan, M. L., Simmons, R. L., and Billiar, T. (1993). Endogenous nitric oxide inhibits the synthesis of cyclooxygenase products and interleukin-6 by rat Kupffer cells. J. Leukocyte Biol. 53, 165-172. 

In healthy humans, inhaled LTC and LTD are more potent than histamine at causing a decrease in maximum e iratory flow rate. effect of LTD. is independent of the production of cyclooxygenase products. In contrast to airway hypersensitivity to histamine among human asthmatics, there is no increased sensitivity to inhaled LTD. ... 

The importance of cyclooxygenase products, particularly thromboxane A, in the bronchospastic response to leukotrienes depends on the species... 

Intravenous or aerosol administration of LTB to guinea pigs produces a bronchospasm. These vitro and in vivo effects of LTB are secondary to the generation of cyclooxygenase products. 

Regulation of fungal morphogenesis by lipoxygenase and cyclooxygenase products... 

Hong JF, Rodger IW, Fee FY (1995) Cigarette smoke-induced bronchoconstriction Cholinergic mechanisms, tachykinins, and cyclooxygenase products, J Appl Physiol 78 2260-2266... 

Reed MW, Weiman TJ, Doak KW, Peitsch CG, Schuschke DA. The microvascular effects of photodynamic therapy evidence for a possible role of cyclooxygenase products. Photochem Photobiol 1989 50 419-423. 

Chen, L.Y., Lawson, D.L., and Mehta, J.L. (1994) Reduction in Human Neutrophil Superoxide Anion Generation by n-3 Polyunsaturated Fatty Acids Role of Cyclooxygenase Products and Endothelium-Derived Relaxing Factor, Thromb. Res. 76,317-322. 

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