Gradual increase of high mobility group protein b1 in the lungs after the onset of acute exacerbation of idiopathic pulmonary fibrosis.

Gradual increase of high mobility group protein b1 in the lungs after the onset of acute exacerbation of idiopathic pulmonary fibrosis.
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DOI:
10.1155/2011/916486
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发表时间:
2011
期刊:
影响因子:
4.3
通讯作者:
Nukiwa T
Nukiwa T
中科院分区:
其他
文献类型:
--
作者:
Ebina M;Taniguchi H;Miyasho T;Yamada S;Shibata N;Ohta H;Hisata S;Ohkouchi S;Tamada T;Nishimura H;Ishizaka A;Maruyama I;Okada Y;Takashi K;Nukiwa T

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特发性肺纤维化(IPF)急性加重的发病机制仍有待阐明。为了评价炎症介质在急性加重中的作用,测定了7例IPF患者急性加重后支气管肺泡灌洗液中高迁移率族蛋白B1(HMGB 1)(急性肺损伤的主要介质)和18种炎性细胞因子的浓度。HMGB 1在急性加重发作后逐渐增加,与单核细胞趋化蛋白-1(MCP-1)(一种有效的纤维化介质)呈正相关。在急性加重后尸检的8例IPF患者的肺组织中,在肺泡毛细血管增强病变的肺泡上皮细胞中观察到HMGB 1的强烈细胞质染色,其中毛细血管内皮细胞显著降低血栓调节蛋白(HMGB 1的内源性拮抗剂)的表达。这些结果表明HMGB 1和MCP-1在IPF急性加重晚期的致病作用。
The pathogenesis of acute exacerbation of idiopathic pulmonary fibrosis (IPF) remains to be elucidated. To evaluate the roles of inflammatory mediators in acute exacerbation, the concentrations of high mobility group protein B1 (HMGB1), a chief mediator of acute lung injury, and 18 inflammatory cytokines were measured in the bronchoalveolar lavage fluid, serially sampled from seven IPF patients after the onset of acute exacerbation. HMGB1 gradually increased in the alveolar fluid after the onset of acute exacerbation, in positive correlation with monocytes chemotactic protein-1 (MCP-1), a potent fibrogenic mediator. In the lung tissues of eight IPF patients autopsied after acute exacerbation, intense cytoplasmic staining for HMGB1 was observed in the alveolar epithelial cells in alveolar capillary augmented lesions, where the capillary endothelial cells remarkably reduced the expression of thrombomodulin, an intrinsic antagonist of HMGB1. These results suggest pathogenic roles for HMGB1 and MCP-1 in the late phase of acute exacerbation of IPF.