Is there a role for specialized pro-resolving mediators in pulmonary fibrosis?

Inhaled toxicants drive the onset of and exacerbate pre-existing chronic pulmonary diseases, however, the biological mechanisms by which this occurs are largely unknown. Exposure to inhaled toxicants, both environmental and occupational, drives pulmonary inflammation and injury. Upon activation of the inflammatory response, polyunsaturated fatty acids (PUFAs) are metabolized into predominately proinflammatory lipid mediators termed eicosanoids which recruit immune cells to the site of injury, perpetuating inflammation to clear the exposed toxicants. Following inflammation, lipid mediator class–switching occurs, a process that leads to increased metabolism of hydroxylated derivates of PUFAs. These mediators, which include mono-hydroxylated PUFA derivatives and specialized pro-resolving lipid mediators (SPMs). These mediators initiate an active process of inflammation resolution by inhibiting the inflammatory response and activating resolution pathways to return tissue homeostasis. Exposure to inhaled toxicants leads to alterations in the synthesis of these pro-inflammatory and pro-resolving lipid mediator pathways, resulting in greater pulmonary inflammation and injury, and increasing the risk for the onset of chronic lung diseases. Recent studies have begun utilizing supplementation of PUFAs and their metabolites as potential therapeutics for toxicant-induced pulmonary inflammation and injury. Here we will review the current understandings of the lipid mediators in pulmonary inflammation and resolution as well as the impact of fatty acid dietary supplementation on lipid mediator driven inflammation following air pollution exposure.

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Is there a role for specialized pro-resolving mediators in pulmonary fibrosis?

Cited by 3 publications

References 166 publications

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Harnessing anti-inflammatory pathways and macrophage nano delivery to treat inflammatory and fibrotic disorders

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Inhaled toxicants and pulmonary lipid metabolism: biological consequences and therapeutic interventions

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