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sPLA2-IIA inhibitor Tricyclic Dipyrido Diazepinone derivative 6 f suppresses poultry organic dust-induced pulmonary inflammation by downregulating ERK1/2-cPLA2 pathway
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DOI：10.1016/j.biopha.2025.118869.png)
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Abstract
En 中文
• This study addresses the effect of poultry organic dust in eliciting lung inflammation, a considerable risk factor for poultry farm workers. • sPLA2-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 sPLA2-IIA mediated MAP kinases and, increased pro inflammatory cytokines and chemokines and lipid mediators. • Pharmacologically, inhibiting sPLA2-IIA with Tricyclic Dipyrido Diazepinone derivative 6 f reduced the lung inflammation by attenuating ERK1/2,P38 & cPLA2 pathway and inhibiting pro-inflammatory mediators.
Keywords:
TDD
Tricyclic Dipyrido Diazepinone
sPLA2-IIA
Secretory Phospholipase A2 group IIA
cPLA2
Cytosolic Phospholipase A2
ODE
Organic Dust Extract
PBS
Phosphate buffered saline
BSA
Bovine Serum Albumin
BALF
Bronchoalveolar Lavage fluid
HPF
Human Pleural Fluid
HSF
Human Synovial Fluid
MTT
3–4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide
COX-2
Cyclooxygenase-2
PGE2
Prostaglandin E2
ERK1/2
Extracellular signal-regulated kinase 1/2
MAPK
Mitogen Activated Protein Kinases
AA
Arachidonic acid
PKC
Protein Kinase C
TNF-α
Tumor Necrosis Factor-alpha
IL-6/8
Interleukin 6 & 8
MIP-1 α/CCL3
Macrophage Inflammatory Protein-1 Alpha Chemokine (C-C motif ligand 3)
MCP-1/CCL-2
Macrophage Chemoattractant Protein −1 Chemokine (C-C motif ligand 2)
RANTES/CCL-5
Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted Chemokine (C-C motif ligand 5)
Lung inflammation
organic dust extract
sPLA2-IIA
Tricyclic Dipyrido Diazepinone
cPLA2
prostaglandins
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Journal
B
IF:
7.5
Papers:
1.6W
Citations:
8.2W
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