Figure 1.

The potential mechanisms of aspirin action in N-ERD. (A) Aspirin acetylates and completely inhibits COX-1. As a result of long-term, high-dose aspirin treatment, there is a reduction in the level of PGD₂. (B) Aspirin acetylates COX-2. Acetylation of COX-2 results in the production of 15(R)-HETE, leading to generation of 15-epi-lipoxins from arachidonic acid and resolvins from DHA and EPA. Lipoxins and resolvins bind to ALX/FPR2 on ILC2, T, B, and NK cells leading to decreased inflammation. Lipoxins also exert antifibrotic effects by reducing the expression of VEGF.  Resolvins act on ALX/FPR2 on macrophages and PMN and promote the resolution of the allergic reaction. (C) Aspirin may inhibit the activation of NF-κB. Aspirin potentially binds to IKK-β (IκB Kinase) and inhibits the degradation of IκB, resulting in inhibition of the NF-κB pathway.  (D) Inhibition of high mobility group box 1 protein (HMGB1). Aspirin directly binds and inhibits HMGB1 and subsequently leads to the inhibition of the downstream pro-inflammatory activating signaling pathway via NF-ĸB. DHA, Docosahexaenoic acid; EPA, Eicosapentaenoic acid; ILC2, innate lymphoid type 2 cells; M, macrophage; L, lymphocyte; NK. Natural Killer; PMN, Polymorphonuclear; UB, ubiquitin; P, Phosphate.