Amenomori Misato, Mukae Hiroshi, Ishimatsu Yuji, Sakamoto Noriho, Kakugawa Tomoyuki, Hara Atsuko, Hara Shintaro, Fujita Hanako, Ishimoto Hiroshi, Hayashi Tomayoshi, Kohno Shigeru
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Exp Lung Res. 2010 Sep;36(7):411-9. doi: 10.3109/01902141003714049.
alpha-Defensins, antimicrobial peptides produced mainly by neutrophils, have been reported to be associated with a wide variety of lung diseases, including idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and diffuse panbronchiolitis (DPB). In each disease, alpha-defensins are located in different areas, such as around the alveolar septa in IPF and around the airways in CF and DPB, suggesting that alpha-defensins play different roles. Meanwhile, growth factors are known to contribute to IPF, CF, and DPB. alpha-Defensins are known to induce interleukin (IL)-8 in airway epithelial cells, but the effects of alpha-defensins on the release of growth factors from various components in the lung have not been sufficiently investigated. In the present study, the in vitro effects of human neutrophil peptide (HNP)-1 (a subtype of alpha-defensin) on the expressions of IL-8 and growth factors in lung fibroblasts, bronchial epithelial cells, and alveolar epithelial cells were examined. HNP-1 mainly enhanced the expression of IL-8 in epithelial cells, whereas it enhanced transforming growth factor-beta and vascular endothelial growth factor expressions in lung fibroblasts. These results suggest that alpha-defensins play different roles in the pathogenesis of IPF, CF, and DPB according to the location in the lung where the alpha-defensins are mainly produced.
α-防御素是主要由中性粒细胞产生的抗菌肽,据报道它与多种肺部疾病有关,包括特发性肺纤维化(IPF)、囊性纤维化(CF)和弥漫性泛细支气管炎(DPB)。在每种疾病中,α-防御素位于不同区域,如IPF中的肺泡间隔周围以及CF和DPB中的气道周围,这表明α-防御素发挥着不同作用。同时,已知生长因子与IPF、CF和DPB有关。已知α-防御素可诱导气道上皮细胞产生白细胞介素(IL)-8,但α-防御素对肺中各种成分释放生长因子的影响尚未得到充分研究。在本研究中,检测了人中性粒细胞肽(HNP)-1(α-防御素的一种亚型)对肺成纤维细胞、支气管上皮细胞和肺泡上皮细胞中IL-8和生长因子表达的体外影响。HNP-1主要增强上皮细胞中IL-8的表达,而增强肺成纤维细胞中转化生长因子-β和血管内皮生长因子的表达。这些结果表明,α-防御素根据其在肺中主要产生的位置,在IPF、CF和DPB的发病机制中发挥不同作用。