B lymphocytes are critical for lung fibrosis control and prostaglandin E2 regulation in IL-9 transgenic mice
B lymphocytes are critical for lung fibrosis control and prostaglandin E2 regulation in IL-9 transgenic mice
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DOI：
10.1165/rcmb.2004-0383oc
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发表时间：
2006-05-01
影响因子：
6.4
通讯作者：
Huaux, F
中科院分区：
文献类型：
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作者：
Arras, M;Louahed, J;Huaux, F
我们先前表明IL-9的过表达控制小鼠中二氧化硅颗粒诱导的肺纤维化（Arras和同事; Am J Respir Cell Mol Biol 2001;24：368-375）。这种保护作用与肺B淋巴细胞的扩增有关。为了探索这些细胞在IL-9的保护作用中的贡献，我们将IL-9转基因（IL-9（+））和B缺陷（B-）小鼠杂交。IL-9的抗纤维化作用在B淋巴细胞缺陷的小鼠（B-IL 9（+））中被消除，并且通过用B淋巴细胞重建这些小鼠而恢复。抗纤维化介质前列腺素（PG）E2的表达在IL-9（+）小鼠的肺中在基线时显著增加，并且在二氧化硅处理后在野生型和转基因品系中发现类似的高水平。这种PGE 2表达在B-小鼠中完全消除，无论是在基线还是在二氧化硅给药后。在体外实验中，IL-9（+）小鼠的肺泡和腹腔巨噬细胞对LIPS或二氧化硅产生PGE 2的能力增加。这种能力在从B-小鼠获得的巨噬细胞中显著降低，并通过将巨噬细胞与来自IL-9+小鼠的B淋巴细胞共孵育而恢复。基于转录分析和NS 398的抑制，IL 9（+）巨噬细胞的PGE 2反应增加依赖于环氧化酶2的表达。我们的结论是，B淋巴细胞是必不可少的保护肺纤维化和巨噬细胞过度表达的PGE 2在IL-9转基因动物。
We previously showed that overexpression of IL-9 controls lung fibrosis induced by silica particles in mice (Arras and colleagues; Am J Respir Cell Mol Biol 2001;24:368-375). This protection was associated with an expansion of lung B lymphocytes. To explore the contribution of these cells in the protective effect of IL-9, we crossed IL-9 transgenic (IL-9(+)) and B-deficient (B-) mice. The antifibrotic effect of IL-9 was abolished in mice deficient in B lymphocytes (B-IL9(+)) and restored by reconstituting these mice with B lymphocytes. The expression of the antifibrotic mediator prostaglandin (PG)E2 was markedly increased in the lung of IL-9(+) mice at baseline, and similarly high levels were found in both wild-type and transgenic strains upon silica treatment. This PGE2 expression was completely abolished in B- mice, both at baseline and upon silica administration. In vitro, alveolar and peritoneal macrophages from IL-9(+) mice had an increased capacity to produce PGE2 in response to LIPS or silica. This capacity was markedly reduced in macrophages obtained from B- mice and restored by co-incubating macrophages with B lymphocytes from IL-9+ mice. The increased PGE2 response of IL9(+) macrophages was dependent on cyclooxygenase 2 expression, based on transcript analysis and inhibition by NS398. We conclude that B lymphocytes are essential for the protection against lung fibrosis and macrophage overexpression of PGE2 in IL-9 transgenic animals.