ENaC dysregulation caused by pro-inflammatory cytokines, such as tumor necrosis factor-a, transforming growth factor-[sz]1, interleukin-1[sz] (IL-1[sz]), IL-4, and IL-13, is primarily responsible for lung edema. Lipoxins
(LXs), a group of endogenous lipids, can alleviate inflammation and show great therapeutic potential in lung edema.
12-LOX and 15-LOX play roles in the production of lipoxins
The other pathway through which arachidonic acid can be metabolized is through lipoxygenase (LOX) enzymes (5-LOX, 8-LOX, 15LOX, and 12-LOX, the latter being implicated in tumorigenesis) inducing synthesis of leukotrienes, lipoxins
, and fatty acids [118, 119].
Borgeson et al., "Lipoxins
attenuate renal fibrosis by inducing let-7c and suppressing TGF[beta]R1," Journal of the American Society of Nephrology, vol.
Recently, several endogenous proresolving lipid mediators have been discovered, including lipoxins
, resolvins, protectins, and maresins, which are heavily involved in driving inflammatory resolution and successfully terminating inflammation [7,8].
In addition, neutrophils degrade inflammatory cytokines by aggregated NETs, secrete soluble factors, including azurocidin, cathepsin G, lipoxins
, and lysophosphatidylserine, and are able to reprogramme macrophages to the regulatory M2 phenotype [6, 12-15].
(24,25) SPMs include lipoxins
, resolvins, protectins and maresins and are known to act as potent regulators of neutrophil infiltration, cytokine and chemokine production, and clearance of apoptotic neutrophils by macrophages which promote the return of tissue homeostasis.
Lipoxygenase (LOX) converts AA, linoleic and other polyunsaturated fatty acids into biologically active metabolites called leukotrienes, hydroxyeicosatetraoneoic acids and lipoxins
(Shureigi and Lippman, 2001).
Arachidonic acid is a precursor of prostaglandins, leukotrienes, thromboxanes and lipoxins
, which in turn act as mediator of platelet function and of inflammatory, vascular, motor and sensory processes, among others.
The transcellular biosynthesis of lipoxins
requires interactions between LOX isoenzymes (LOX-LOX interactions) and can promote generation of leukotrienes (LTs) by endothelial cells .
Trubiani et al., "Human periodontal stem cells release specialized proresolving mediators and carry immunomodulatory and prohealing properties regulated by lipoxins
," Stem Cells Translational Medicine, vol.
These SPMs are distinguished in different distinct families, including the omega-6 PUFA-derived lipoxins
, and the omega-3 PUFA-derived D-series resolvins, E-series resolvins, protectins, and maresins .