Abstract
The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferator-activated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.
Highlights
Asthma is a commonly occurring chronic inflammatory disease with high variability due to the influence of genetic and environmental factors [1, 2]
Peroxisome proliferator-activated receptors (PPARs) inhibit the proinflammatory activity of NF-κB as a major regulator of innate and adaptive immune responses in asthma [72]. This factor plays an important role in the regulation of T helper 2 cell (Th2) cytokine production, mucus hyperproduction, and airway remodeling processes involved in asthma pathogenesis [73]
The activation of receptors expressed on the cell membrane by allergens is accompanied by the formation of the Th2 immune response and the development of allergic inflammation [76]
Summary
Asthma is a commonly occurring chronic inflammatory disease with high variability due to the influence of genetic and environmental factors [1, 2]. Despite the effectiveness of traditional methods of asthma treatment, a number of patients have exacerbations and progressive deterioration of pulmonary function It can be accounted for by the heterogeneity of the disease and the complexity of pathogenetic mechanisms. The correction of disorders in PPAR Research the signaling pathways involved in immune response and lipid metabolism in asthma provides many opportunities to improve the methods of the treatment of the disease. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of inflammatory reactions and lipid metabolism. The study of therapeutic efficiency of natural PPAR agonists (polyunsaturated fatty acids (PUFAs), eicosanoids, endocannabinoids, and endogenous specialized proresolving mediators (SPMs)) with a lower number of side effects than that of synthetic ones may be an incentive to develop a new combined therapy of asthma. The possibility to use PPARs as a therapeutic target in asthma has been described
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