Innate immunity is a key factor for the resolution of inflammation in asthma

Abstract

The resolution of inflammation is an integral and natural part of the physiological response to tissue injury, infection and allergens or other noxious stimuli. Resolution is now recognised as an active process with highly regulated cellular and biochemical events. Recent discoveries have highlighted that innate inflammatory cells have bimodal effector functions during the inflammatory response, including active roles during the resolution process. Several mediators displaying potent pro-resolving actions have recently been uncovered. Lipoxin A4, the lead member of this new class of pro-resolving mediators, has anti-inflammatory actions on type 2 innate lymphoid cells and pro-resolving actions through natural killer cells in asthma immunobiology. Eosinophils are also able to control crucial aspects of resolution through the generation of pro-resolving mediators. Uncontrolled asthma has been associated with a defect in thegeneration of specialised pro-resolving mediators, including lipoxin A4 and protectin D1. Thus, bioactive stable analogue mimetics of these mediators that can harness endogenous resolution mechanisms for inflammation may offer new therapeutic strategies for asthma and airway inflammation associated diseases.

Association between psoriasis and asthma risk: A meta-analysis

“…Asthma is a chronic inflammatory disorder of the airway that is caused by multiple factors that involve environmental, genetic, and immunologic factors. 5,6 It is now thought that asthma may not solely be controlled by the Th2 subset but that a variety of T cells and cytokines are involved in the pathogenesis of asthma. 16,17 Th2 cells have been shown to play a critical role in the pathogenesis of eosinophilic asthma by producing IL-4, IL-5, and IL-13 cytokines; whereas Th1 cells, especially Th17 cells, are mainly involved in the pathogenesis of neutrophilic asthma, and the differentiation and activation of Th17 cells require the presence of cytokines, including IL-1␤, IL-6, transforming growth factor ␤ and IL-23.…”

“…2,4 The complex causes of asthma likely depend on the interaction of environmental, immunologic, and genetic factors. 5,6 Two studies found that asthma is associated with allergic rhinitis, gastrointestinal symptoms, obesity, and psoriasis. 7,8 Psoriasis is a chronic, immune-mediated inflammatory disease of the skin and/or joints, 9 and its prevalence varies in different populations.…”

Anti-Inflammatory Effects of OxPAPC Involve Endothelial Cell–Mediated Generation of LXA4

“…This process involves sequential combination of 15-LO, 5-LO, and epoxide hydrolase activities 42 expressed by different cell types and therefore requiring cell–cell interactions at sites of inflammation. Although LXA4 is present in low abundance during the initiation of acute inflammation, their levels increase substantially during resolution 49–51 . LXA4, in turn, exhibits multi-facet modalities in suppressing inflammation and promoting lung repair 19 including a novel mechanism for control of vascular endothelial inflammation by changes in lung micromechanics recently described by our group 18 .…”

G Protein–Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action

“…However, we would also like to point out that there are a number of other promising GPCR modulators in the early development for asthma. Those include bitter taste receptor agonists such as saccharin, chloroquine, and quinine (Deshpande et al, 2010;Grassin-Delyle et al, 2013); calcium-sensing receptor antagonists (Yarova et al, 2015); and specialized proresolving lipid mediators (SPMs) ( Barnig and Levy, 2015). They may as well offer exciting opportunities for the development of novel asthma therapeutics (Pera and Penn, 2016).…”