Blockade of Airway Inflammation by Kaempferol via Disturbing Tyk-STAT Signaling in Airway Epithelial Cells and in Asthmatic Mice

• Published in: Evidence-based complementary and alternative medicine Vol. 2013; no. 2013; pp. 1 - 13
• Main Authors: Shin, Daekeun, Park, Sin-Hye, Gong, Ju-Hyun, Kang, Young-Hee, Kim, Jung-Lye, Kang, Min-Kyung, Han, Seon-Young
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Puplishing Corporation 01.01.2013; Hindawi Publishing Corporation; Hindawi Limited
• Subjects: Activation; Asthma; Berries; Chemical compounds; Chemokines; CXCR2 protein; Cytokines; Eosinophilia; Eotaxin; Epidermal growth factor; Epithelial cells; Epithelium; Flight corridors; Fruits; Inflammation; Interleukin 8; Kaempferol; Kinases; Lipopolysaccharides; Macrophage inflammatory protein; Mice; Oral administration; Ovalbumin; Pathogenesis; Penicillin; Respiratory tract; Respiratory tract diseases; Stat1 protein; Stat3 protein; TLR4 protein; Toll-like receptors; Tyk2 protein; United States > US
• ISSN: 1741-427X; 1741-4288
• DOI: 10.1155/2013/250725

Asthma is characterized by bronchial inflammation causing increased airway hyperresponsiveness and eosinophilia. The interaction between airway epithelium and inflammatory mediators plays a key role in the asthmatic pathogenesis. The in vitro study elucidated inhibitory effects of kaempferol, a flavonoid found in apples and many berries, on inflammation in human airway epithelial BEAS-2B cells. Nontoxic kaempferol at ≤20 μM suppressed the LPS-induced IL-8 production through the TLR4 activation, inhibiting eotaxin-1 induction. The in vivo study explored the demoting effects of kaempferol on asthmatic inflammation in BALB/c mice sensitized with ovalbumin (OVA). Mouse macrophage inflammatory protein-2 production and CXCR2 expression were upregulated in OVA-challenged mice, which was attenuated by oral administration of ≥10 mg/kg kaempferol. Kaempferol allayed the airway tissue levels of eotaxin-1 and eotaxin receptor CCR3 enhanced by OVA challenge. This study further explored the blockade of Tyk-STAT signaling by kaempferol in both LPS-stimulated BEAS-2B cells and OVA-challenged mice. LPS activated Tyk2 responsible for eotaxin-1 induction, while kaempferol dose-dependently inhibited LPS- or IL-8-inflamed Tyk2 activation. Similar inhibition of Tyk2 activation by kaempferol was observed in OVA-induced mice. Additionally, LPS stimulated the activation of STAT1/3 signaling concomitant with downregulated expression of Tyk-inhibiting SOCS3. In contrast, kaempferol encumbered STAT1/3 signaling with restoration of SOCS3 expression. Consistently, oral administration of kaempferol blocked STAT3 transactivation elevated by OVA challenge. These results demonstrate that kaempferol alleviated airway inflammation through modulating Tyk2-STAT1/3 signaling responsive to IL-8 in endotoxin-exposed airway epithelium and in asthmatic mice. Therefore, kaempferol may be a therapeutic agent targeting asthmatic diseases.