Pro-Resolving Lipid Mediators in the Pathophysiology of Asthma

Abstract

Asthma is one of the most important medical and social problems of our time due to the prevalence and the complexity of its treatment. Chronic inflammation that is characteristic of asthma is accompanied by bronchial obstruction, which involves various lipid mediators produced from n-6 and n-3 polyunsaturated fatty acids (PUFAs). The review is devoted to modern ideas about the PUFA metabolites—eicosanoids (leukotrienes, prostaglandins, thromboxanes) and specialized pro-resolving lipid mediators (SPMs) maresins, lipoxins, resolvins, protectins. The latest advances in clinical lipidomics for identifying and disclosing the mechanism of synthesis and the biological action of SPMs have been given. The current views on the peculiarities of the inflammatory reaction in asthma and the role of highly specialized metabolites of arachidonic, eicosapentaenoic and docosahexaenoic acids in this process have been described. The possibility of using SPMs as therapeutic agents aimed at controlling the resolution of inflammation in asthma is discussed.

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

“…Eicosanoids are proinflammatory lipid mediators, including the prostanoid family: PG (PG12, PGF2, PGD2, and PGE2), cyclopentenone PG (15d-PGJ2, Δ12-PGJ2, PGJ2, PGC2, PGA1, and PGA2), and thromboxane A2 (TxA2); the LT family (LTC4, LTD4, LTE4, LTF4, LTD4, LTA4, and LTB4); and the eoxin family (A4, C4, D4, and E4) [100]. Eicosanoids play a key role in the initiation of the acute inflammatory process [101][102][103][104][105][106][107][108][109][110] (see Table 2).…”

“…The production of PGE2 and PGD2 is known to increase in the inflammation; they are transformed into antiinflammatory PGA2 and 15d-PGJ2 [94]. Besides, the resolution of acute inflammation is the process of switching the synthesis of proinflammatory lipid mediators (PG, LT) to the formation of endogenous SPMs [110]. The precursors of SPMs are PUFAs.…”

“…SPM. In both AA and DHA, EPA can act as precursors for the production of SPMs involved in the resolution of inflammation, which include Rvs (RvE (RvE1, RvE2), RvD (RvD1, RvD2, RvD3, RvD4, RvD5, and RvD6), and RvT (RvT1, RvT2, RvT3, and RvT4)), LXs (LXA4, LXВ4), PDs (РD1), and MaRs (МaR1, MaR2) [110,116]. Proresolving lipid mediators and their lung functions are presented in Table 3.…”

“…The study of proresolving lipid mediators, which are PPAR agonists, opens up new ways for the development of an effective strategy for asthma treatment by correcting the processes of the inflammation resolution [110,129].…”

Use of DAMPs and SAMPs as Therapeutic Targets or Therapeutics: A Note of Caution

“…Moreover, the pathogenetic involvement of these molecules qualifies them as relevant drug targets or therapeutics as well. Indeed, accumulating preclinical data have encouraged envisaging DAMPs as therapeutic targets for inhibition [5,[12][13][14][15][16][17] and administration of SAMPs as candidate drugs [5,[18][19][20][21][22][23][24][25][26][27] for treating acute or chronic inflammatory disorders. On the other hand, DAMPs may also be…”