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Review
. 2008 Jun;133(6):1442-1450.
doi: 10.1378/chest.08-0306.

Eicosanoid lipid mediators in fibrotic lung diseases: ready for prime time?

Steven K Huang  1 , Marc Peters-Golden  2
Affiliations
Review

Eicosanoid lipid mediators in fibrotic lung diseases: ready for prime time?

Steven K Huang et al. Chest. 2008 Jun.

Abstract

Recognition of a pivotal role for eicosanoids in both normal and pathologic fibroproliferation is long overdue. These lipid mediators have the ability to regulate all cell types and nearly all pathways relevant to fibrotic lung disorders. Abnormal fibroproliferation is characterized by an excess of profibrotic leukotrienes and a deficiency of antifibrotic prostaglandins. The relevance of an eicosanoid imbalance is pertinent to diseases involving the parenchymal, airway, and vascular compartments of the lung, and is supported by studies conducted both in humans and animal models. Given the lack of effective alternatives, and the existing and emerging options for therapeutic targeting of eicosanoids, such treatments are ready for prime time.

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Conflict of interest statement

Dr. Peters-Golden declares no conflict of interest.

Dr. Huang declares no conflict of interest.

Figures

Fig 1
Fig 1. Eicosanoid synthesis and receptors
Arachidonic acid, released from membrane phospholipids by cytosolic phospholipase A2 (cPLA2), can be metabolized by the 5-lipoxygenase (5-LO) pathway to make leukotrienes (LT) or by the cyclooxygenase pathway (COX) to make prostaglandins (PG). Terminal synthases complete the biosynthesis of specific eicosanoid products. Eicosanoids exert their actions via binding to 7-transmembrane G-protein coupled receptors and subsequent intracellular signaling. FLAP = 5-LO activating protein.
Fig 2
Fig 2. Crosstalk between eicosanoids and other mediators
During normal homeostatic conditions, lung levels of PGs exceed LT levels. However, abnormal fibroproliferation is characterized by a synthetic imbalance favoring LTs over PGs. Moreover, other mediators known to play important roles in modulating fibrogenesis can regulate, or be regulated, by LTs or PGs. Arrows indicate stimulatory effects and minus signs indicate inhibitory effects.
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