Eicosanoids in asthma.
Eicosanoids belong to a diverse family of bioactive fatty acids that play important roles in regulating airway inflammation and reactivity. They are the key mediators of the pathobiology of asthma. Among the eicosanoids, lipoxins (LXs) were the first agents to be identified and recognized as potential anti-inflammatory endogenous lipid mediators. Lipoxins are biosynthesized in vivo at inflammation sites. They result mainly from the interaction between 5 and 15-lipoxygenases (LOs), which are distinct from leukotrienes (LTs) and prostaglandins (PGs) in structure and function. Leukotrienes are potent proinflammatory mediators and directly and indirectly stimulate fibroblast chemotaxis, proliferation, and collagen synthesis. Prostaglandins have both bronchoconstrictive and bronchoprotective effects and the bronchoconstriction mediated by PGD2 and PGF2alpha is only occurred in asthmatic patients but not in healthy subjects. Lipoxins counter-regulate the proinflammatory actions of LTs and activate resolution of the inflammatory response. At least two classes of receptors, CysLT1 receptors and Asprin-triggered lipoxin A4 (ALX) receptors, can interact with lipoxin A4 (LXA4) and LXA4 analogs to mediate their biologic actions. Allergen challenge initiates airway biosynthesis of LXA4 and increases expression of its receptor. In addition, LXA4 affects the release of interleukin-8 by blood mononuclear cells, and ALX affects calcium influx into epithelial cells. Therefore, the pivotal role of LXs is mediating airway homeostasis, and LXs may be part of a novel, multipronged approach for treating human asthma.
Wan
Kong-Sang
KS
Department of Pediatrics, Taipei City Hospital, Ren-ai Branch, Taipei, Taiwan. DXD40@tpech.gov.tw
Wu
Wei-Fong
WF
D001249:Asthma / Q000209:etiology*; D015777:Eicosanoids / Q000502:physiology*; D006801:Humans; D015289:Leukotrienes / Q000502:physiology; D044045:Lipoxins / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology
D015777:Eicosanoids; D015289:Leukotrienes; D044045:Lipoxins; D011453:Prostaglandins