Bone morphogenetic protein 4 inhibits liposaccharide-induced inflammation in the airway

作者：Li Zhengtu; Wang Jian; Wang Yan; Jiang Hua; Xu Xiaoming; Zhang Chenting; Li Defu; Xu Chuyi; Zhang Kedong; Qi Yafei; Gong Xuefang; Tang Chun; Zhong Nanshan; Lu Wenju^*

来源：European Journal of Immunology, 2014, 44(11): 3283-3294.

DOI：10.1002/eji.201344287

• Airway inflammation
• BMP4
• LPS
• Lung function
• Pseudomonas aeruginosa

Bone morphogenetic protein 4 (BMP4) is a multifunctional growth factor that belongs to the TGF- superfamily. The role of BMP4 in lung diseases is not fully understood. Here, we demonstrate that BMP4 was upregulated in lungs undergoing lipopolysaccharide (LPS)-induced inflammation, and in airway epithelial cells treated with LPS or TNF-. BMP4 mutant (BMP4(+/-)) mice presented with more severe lung inflammation in response to LPS or Pseudomonas aeruginosa, and lower bacterial load compared with that in BMP4(+/+) mice. Knockdown of BMP4 by siRNA increased LPS and TNF--induced IL-8 expression in 16HBE human airway epithelial cells and in primary human bronchial epithelial cells. Similarly, peritoneal macrophages from BMP4(+/-) mice produced greater levels of TNF- and keratinocyte chemoattractant (KC) upon LPS treatment compared with cells from BMP4(+/+) mice. Administration of exogenous BMP4 attenuated the upregulation of TNF-, IL-8, or KC induced by LPS and/or TNF- in airway epithelial cells, and peritoneal macrophages. Finally, partial deficiency of BMP4 in BMP4(+/-) mice protected the animals from restrictive lung function reduction upon chronic LPS exposure. These results indicate that BMP4 plays an important anti-inflammatory role, controlling the strength and facilitating the resolution of acute lung inflammation; yet, BMP4 also contributes to lung function impairment during chronic lung inflammation.

• 单位
  1; 广州医学院