Kaempferol ameliorates airway inflammation through Tyk2‐STAT1/3 signaling in human airway epithelial cells and ovalbumin‐challenged mice: role of interleukin‐8

Allergic asthma is characterized by bronchial airway inflammation resulting in increased airway hyperresponsiveness, eosinophilia and mucus hyperproduction. The interaction between the airway epithelium and inflammatory mediators plays a key role in the pathogenesis of allergic asthma. The in vitro study elucidated inhibitory effects of kaempferol, a flavonoid with anti‐inflammatory activity, on LPS or IL‐8‐induced airway inflammation in BEAS‐2B cells. Nontoxic kaempferol at ≤20 μM significantly inhibited the LPS‐induced IL‐8 production through the TLR4 activation, resulting in eotaxin‐1 induction. In addition, kaempferol attenuated Tyk2 phosphorylation and STAT1/3 activation following IL‐8 secretion by LPS, and further enhanced the Tyk activation‐inhibiting SOCS3 expression. The in vivo study explored demoting effects of kaempferol on asthmatic responses in BALB/c mice sensitized with ovalbumin (OVA). Oral administration of kaempferol suppressed goblet cell hyperplasia, collagen deposition and mucus secretion in the airway and lung of OVA‐challenged mice via a blockade of STAT3 transactivation. These results demonstrate that dietary kaempferol alleviated airway asthmatic remodeling through modulating Tyk‐STAT signaling responsive to the inflammatory chemokine IL‐8. Therefore, kaempferol may be a potential therapeutic agent targeting inflammatory airway diseases such as asthma.