The role of specialized pro-resolving lipid mediators such as resolvins in immune complex-induced inflammation remains incompletely understood. This study investigates the protective effects of aspirin-triggered (17R) resolvin D1 (AT-RvD1) and its metabolically stable analogue, 17R-hydroxy-19-para-fluorophenoxy-resolvin D1 methyl ester (p-RvD1), in a murine model of IgG immune complex-induced lung injury. Both AT-RvD1 and p-RvD1 significantly reduced lung vascular permeability, as evidenced by decreased albumin leakage into bronchoalveolar lavage fluid (BALF). Treatment with either compound markedly attenuated neutrophil infiltration in BALF, indicating suppression of acute inflammatory cell recruitment. Furthermore, levels of key inflammatory mediators—including TNF-α, IL-6, KC (keratinocyte-derived chemokine), and MIP-1—were significantly reduced in BALF from treated mice compared to controls.
Electrophoretic mobility shift assays revealed that both AT-RvD1 and p-RvD1 inhibited the activation of NF-κB and C/EBP transcription factors in lung tissues following IgG immune complex deposition. These findings were corroborated in alveolar macrophages, where AT-RvD1 suppressed NF-κB and C/EBP promoter-luciferase activity induced by IgG immune complexes. In vitro experiments demonstrated that AT-RvD1 significantly reduced TNF-α, IL-6, KC, and MIP-1 secretion from IgG-stimulated alveolar macrophages and primary neutrophils. Notably, both compounds substantially lowered BALF levels of complement C5a, a potent chemoattractant and activator of inflammatory cells.Thio-TEPA Activator The inhibition of C5a production suggests a mechanism by which resolvins disrupt the amplification loop of inflammation.3-Iodopropionic acid In Vivo
These results demonstrate that AT-RvD1 and p-RvD1 exert robust anti-inflammatory and pro-resolving actions in IgG immune complex-mediated lung injury.PMID:35107739 Their ability to suppress transcription factor activation, cytokine and chemokine release, and C5a generation highlights their potential as therapeutic agents for conditions involving immune complex deposition, including autoimmune diseases and hypersensitivity pneumonitis. Targeting resolution pathways with stable resolvin analogues may offer a novel strategy to control excessive inflammation while promoting tissue repair.
Keywords: Resolvin D1; Lung; Immune Complex; Inflammation; Resolution; C5a; NF-κB; C/EBPMedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com