Resolvin D1 protects mice from LPS-induced acute lung injury.
ABSTRACT Resolvin D1 (RvD1), an endogenous lipid molecule derived from docosahexaenoic acid (DHA), has been described to promote inflammatory resolution. The present study aimed to determine the protective effects and the underlying mechanisms of RvD1 on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Pretreatment RvD1 to mice 30 min before inducing ALI by LPS decreased the mortality and improved lung pathological changes, inhibited LPS-induced increases in polymorphonulear and mononuclear leukocytes recruitment, total proteins content, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) production in the bronchoalveolar lavage fluids (BALFs). In addition, RvD1 markedly reduced LPS-induced the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and adhesion molecules, as well as myeloperoxidase (MPO) activity. Moreover, RvD1 markedly inhibited LPS-induced the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB). Furthermore, pretreatment with Boc, a lipoxin A4 receptor (ALX) antagonist, significantly reversed these beneficial effects of RvD1 on LPS-induced acute lung injury in mice. Taken together, our study showed that RvD1 improved survival rate and attenuated ALI in mice induced by LPS, and the protective mechanisms might be related to selective reaction with ALX, which inhibits MAPKs and NF-κB pathway.
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ABSTRACT: Mucosal surfaces function as selectively permeable barriers between the host and the outside world. Given their close proximity to microbial Ags, mucosal surfaces have evolved sophisticated mechanisms for maintaining homeostasis and preventing excessive acute inflammatory reactions. The role attributed to epithelial cells was historically limited to serving as a selective barrier; in recent years, numerous findings implicate an active role of the epithelium with proresolving mediators in the maintenance of immunological equilibrium. In this brief review, we highlight new evidence that the epithelium actively contributes to coordination and resolution of inflammation, principally through the generation of anti-inflammatory and proresolution lipid mediators. These autacoids, derived from ω-6 and ω-3 polyunsaturated fatty acids, are implicated in the initiation, progression, and resolution of acute inflammation and display specific, epithelial-directed actions focused on mucosal homeostasis. We also summarize present knowledge of mechanisms for resolution via regulation of epithelial-derived antimicrobial peptides in response to proresolving lipid mediators.The Journal of Immunology 10/2011; 187(7):3475-81. · 5.52 Impact Factor
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ABSTRACT: Unresolved inflammation is associated with several widely occurring diseases such as arthritis, periodontal diseases, cancer, and atherosclerosis. Endogenous mechanisms that curtail excessive inflammation and prompt its timely resolution are of considerable interest. In recent years, previously unrecognized chemical mediators derived from polyunsaturated fatty acids were identified that control the acute inflammatory response by activating local resolution programs. Among these are the so-called specialized pro-resolving lipid mediators (SPMs) that include lipoxins (LX), resolvins (Rv), protectins (PD), and maresins (MaR), because they are enzymatically biosynthesized during resolution of self-limited inflammation. They each possess distinct chemical structures and regulate cellular pathways by their ability to activate pro-resolving G-protein coupled receptors (GPCRs) in a stereospecific manner. For instance, RvD1 controls several miRNAs of interest in self-limited acute inflammation that counter-regulate the mediators and proteins that are involved in inflammation. Here, we overview some of the biosynthesis and mechanisms of SPM actions with focus on the recently reported miR involved in their pro-resolving responses that underscore their beneficial actions in the regulation of acute inflammation and its timely resolution. The elucidation of these mechanisms operating in vivo to keep acute inflammation within physiologic boundaries as well as stimulate resolution have opened resolution pharmacology and many new opportunities to target inflammation-related human pathologies via activating resolution mechanisms.Frontiers in Immunology 01/2012; 3:298.