sPLA2-IIA inhibitor Tricyclic Dipyrido Diazepinone derivative 6 f suppresses poultry organic dust-induced pulmonary inflammation by downregulating ERK1/2-cPLA2 pathway - 09/01/26
Abstract |
Poultry farm workers are highly susceptible to developing lung inflammatory diseases (asthma, COPD, ARDS, and ALI) due to prolonged exposure to organic dust and other airborne irritants in confined poultry facilities. Secretory phospholipase A2 (sPLA 2 -IIA) is a vital proinflammatory enzyme play an important role in the production of inflammatory mediators. Hence, this study examined the regulatory role of secretory phospholipase A2 enzyme in poultry dust induced lung inflammation in in vitro and in vivo models. Lung epithelial A549 cells and BALB/c mice treated with poultry dust increased the sPLA 2 -IIA mRNA expression and stimulated the induction of inflammatory symptoms. Inhibition of sPLA 2 enzyme activity by Tricyclic Dipyrido Diazepinone derivative 6 f (sPLA 2 inhibitor) markedly ameliorated ODE-induced lung histopathological conditions, decreased lung edema, cellular infiltration, and protein secretion. Further, downregulated activation of cPLA 2 via decreasing phosphorylation of ERK1/2 and p38. Suppressing cPLA 2 signalling cascade significantly reduced the production of inflammatory cytokines (IL-6, IL-8, and TNF-α) and chemokines (MIP-1, MCP, and RANTES). Consequently, the activation of COX-2 and the production of prostaglandin E2 and thromboxane B2 were significantly decreased. Conclusively, these findings indicated that sPLA 2 -IIA could potentially serve as a novel therapeutic target for treating lung inflammation in disease conditions.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Schematic representation of sPLA 2 -IIA–mediated inflammatory signaling and its pharmacological inhibition in organic dust-induced lung inflammation
Schematic representation of sPLA 2 -IIA–mediated inflammatory signaling and its pharmacological inhibition in organic dust-induced lung inflammation Le texte complet de cet article est disponible en PDF.
Highlights |
• | This study addresses the effect of poultry organic dust in eliciting lung inflammation, a considerable risk factor for poultry farm workers. |
• | sPLA 2 -IIA is a crucial inflammatory enzyme in dust-induced airway inflammation by exhibiting elevated gene expression and enzyme activity in lung epithelial cells and mice. |
• | Exposure to poultry organic dust triggered sPLA 2 -IIA mediated MAP kinases and, increased pro inflammatory cytokines and chemokines and lipid mediators. |
• | Pharmacologically, inhibiting sPLA 2 -IIA with Tricyclic Dipyrido Diazepinone derivative 6 f reduced the lung inflammation by attenuating ERK1/2,P38 & cPLA 2 pathway and inhibiting pro-inflammatory mediators. |
Abbreviations : TDD, sPLA 2 -IIA , cPLA 2 , ODE, PBS, BSA, BALF, HPF, HSF, MTT, COX-2, PGE2, ERK1/2, MAPK, AA, PKC, TNF-α, IL-6/8, MIP-1 α/CCL3, MCP-1/CCL-2, RANTES/CCL-5
Keywords : Lung inflammation, organic dust extract, sPLA 2 -IIA , Tricyclic Dipyrido Diazepinone, cPLA 2 , prostaglandins
Plan
Vol 194
Article 118869- janvier 2026 Retour au numéro
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