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Oroxylin‐A suppresses adhesion molecules expression and endothelial barrier disruption in endotoxemic arteries
Author(s) -
Tseng TzuLing,
Chen MeiFang,
Liu ChinHung,
Hsu YungHsaiang,
Lee Tony J. F.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.827.13
Subject(s) - adherens junction , inflammation , proinflammatory cytokine , cell adhesion molecule , endothelial activation , lipopolysaccharide , endothelium , microbiology and biotechnology , endothelial dysfunction , intercellular adhesion molecule , endothelial stem cell , intercellular adhesion molecule 1 , ve cadherin , vascular permeability , immunology , pharmacology , chemistry , cell adhesion , medicine , biology , cadherin , biochemistry , cell , in vitro
Vascular inflammation plays a critical role in the pathogenesis of sepsis, which is characterized by disruption of endothelial junctions, increasing vascular permeability and leakage, and promoting leukocytes and inflammatory exudates to enter the injured area. Here we assess the beneficial effects of post‐treatment of Oroxylin‐A (OroA), a flavonoid, in ameliorating lipopolysaccharide (LPS)‐induced adhesion molecules expression, endothelial barrier dysfunction, and vascular inflammation. Rats were injected with LPS (10 mg/kg, ip) to induce systemic inflammation, and OroA (15 mg/kg, iv) was given 6 hours after LPS treatment. Biochemical changes in the circulation, and morphological/histological alternations associated with inflammation in the aorta were investigated. LPS significantly enhanced proinflammatory cytokines release, increased vascular cell adhesion molecule (VCAM)‐1 and intercellular adhesion molecule (ICAM)‐1 expressions, disrupted endothelial tight junction zona occludens (ZO)‐1 surface expression, reduced stabilization of adherens junction vascular endothelial cadherin (VE‐cadherin) of endothelial barrier, and increased macrophage infiltration and accumulation in aortic arteries. All these changes were reversed by OroA (15 mg/kg, iv) post‐treatment. This post‐treatment also blocked the LPS‐activated aortic NF‐κB. Moreover, this post‐treatment suppressed interleukin‐1‐receptor‐associated‐kinase (IRAK)‐4‐targeted IKKα/β phosphorylation without directly affecting interaction between LPS and toll‐like receptor (TLR)‐4 receptor. These results obtained from studying OroA suggest that beside anti‐inflammation via inhibiting IRAK‐4‐mediated NF‐κB activation, reversal of adhesion molecules expression and endothelial barrier dysfunction may be another useful strategies in managing endotoxemic shock. Support or Funding Information supported by the MOST, Tzu Chi Foundation, Tzu Chi University and Tzu Chi Medical Center