title: Bone morphogenetic protein 4 inhibits liposaccharide-induced inflammation in the airway.
abstract: Bone morphogenetic protein 4 (BMP4) is a multifunctional growth factor that belongs to the TGF-β 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-α. 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-α-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-α and keratinocyte chemoattractant (KC) upon LPS treatment compared with cells from BMP4(+/+) mice. Administration of exogenous BMP4 attenuated the upregulation of TNF-α, IL-8, or KC induced by LPS and/or TNF-α 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.
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Zhengtu
authors.initials: Z
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.forename: Chenting
authors.initials: C
authors.lastname: Zhang
authors.forename: Defu
authors.initials: D
authors.lastname: Li
authors.forename: Chuyi
authors.initials: C
authors.lastname: Xu
authors.forename: Kedong
authors.initials: K
authors.lastname: Zhang
authors.forename: Yafei
authors.initials: Y
authors.lastname: Qi
authors.forename: Xuefang
authors.initials: X
authors.lastname: Gong
authors.forename: Chun
authors.initials: C
authors.lastname: Tang
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
authors.forename: Wenju
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D018836:Inflammation Mediators; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D055370:Lung Injury / Q000517:prevention & control; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000276:immunology; D051785:Smad Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D018836:Inflammation Mediators; D016209:Interleukin-8; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D051785:Smad Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: Airway inflammation; BMP4; LPS; Lung function; Pseudomonas aeruginosa