Enhanced Expression of Cylooxygenase-2(COX-2) In Chronological Skin Aging And Photoaging

Skin aging can be attributed to photoaging (extrinsic) and chronological (intrinsic) aging. Photoaging and intrinsic aging are induced by damage to human skin attributable to repeated exposure to ultraviolet (UV) irradiation and to the passage of time. COX-2 is a key enzyme involved in the development of inflammatory response. Cyclooxygenase-2 (COX-2) is also known as prostaglandin H synthase-2, PGHS-2. The names “prostaglandin synthase (PHS)” and “prostaglandin endoperoxide synthetase (PES)” are still used to refer to COX. Cyclooxygenase (COX) is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. A prostaglandin is any member of a group of lipid compounds – Eicosanoidthat are derived enzymatically from fatty acids. Eicosanoids is a group of lipids including four families —the prostaglandins, prostacyclins, the thromboxanes and the leukotrienes. Eicosanoids are signaling molecules derived from oxidation of the 20-carbon essential fatty acids (EFAs) either omega-3 (ω-3) or omega-6 (ω-6) EFAs. They exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system. The ω-6 eicosanoids are generally pro-inflammatory; ω-3s are much less so. Two families of enzymes catalyze fatty acid oxygenation to produce the eicosanoids:

  • Cyclooxygenase, or COX, generates the prostanoids.
  • Lipoxygenase, or LOX, in several forms. 5-lipoxygenase (5-LO) generates the leukotrienes.

Prostaglandins are produced following the sequential oxidation of arachidonic acid (AA), DGLA or EPA by cyclooxygenases (COX-1 and COX-2) and terminal prostaglandin synthases. COX-1 is responsible for the baseline levels of prostaglandins while COX-2 produces prostaglandins through (environmental) stimuli. Cyclooxygenase-2 or simply COX-2 converts arachidonic acid (AA) to prostaglandin endoperoxide H2. Prostaglandin levels are increased by COX-2 in scenarios of inflammation. Arachidonic acid (AA) is a polyunsaturated omega-6 fatty acid. COX-2 is unexpressed under normal conditions in most cells, but elevated levels are found during inflammation. Prostaglandins are locally acting hormones (autocrine or paracrine) and have a variety of strong physiological effects, such as regulating the contraction and relaxation of smooth muscle tissue. There are currently ten known prostaglandin receptors on various cell types. The diversity of receptors means that prostaglandins act on an array of cells and have a wide variety of effects one of which is regulate inflammatory mediation. Prostanoids (prostaglandins, prostacyclin and thromboxane) mediate local symptoms of inflammation: vasoconstriction or vasodilation, coagulation, pain and fever. Several biologically active metabolites of arachidonic acid including prostaglandins and leukotrienes have been the subjects of studies focusing on the Inflammatory mediators specifically in the skin. The family of polypeptides known as interleukin-1 are also emerging as inflammatory mediators of potential importance in the skin. Such mediators can be quantified in a controlled manner from inflammatory processes in human skin, and the pharmacological and clinical effects of specific enzyme inhibitors can be determined in vivo.

Studies have found the linkage of COX-2 expression level to chronological skin aging and photoaging. Enhanced expression of cylooxygenase-2 by UV in aged human skin was observed. Prostaglandins (PGs) induced by UV may play important roles in UV-induced inflammaging, photocarcinogenesis, and photoaging processes in human skin. The study examined the influence of aging on UV-induced PGE2 production and COX-2 expression in human skin in vivo. It was found that aged human skin produces higher amounts of PGE2 than young skin after exposed to UV. The inductions of COX-2 mRNA and protein by UV in aged skin were higher than those in the young skin, whereas COX-1 mRNA expression remained unchanged. Aged human macrophage expressed higher amounts of PGE2 and COX-2 protein constitutively, and also induced these species after LPS treatment more so than young cells. These data suggest that aged skin may increase susceptibility to the development of photoaging in skin via enhanced PGE2 and COX-2 expression induced by UV radiation

The significance of COX-2 inhibitors have been implicated in anti-aging skin care topical formulations one of which is its substrate competitor EPA. Researches has established the fact that EPA can inhibited UV-induced cyclooxygenase-2 (COX-2) expression without altering COX-1 expression. More discussions about the role of COX-2 inhibitors in inhibit skin’s inflammaging process is available in the post ”

The Two Different Classes of Anti-Inflammatory Ingredients in Wrinkle Creams: COX And 5-LOX Inhibitors


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