Regulation of chemokine expression by NaCl occurs independently of cystic fibrosis transmembrane conductance regulator in macrophages
Regulation of chemokine expression by NaCl occurs independently of cystic fibrosis transmembrane conductance regulator in macrophages
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DOI：
10.2353/ajpath.2006.051042
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发表时间：
2006-07-01
影响因子：
6
通讯作者：
Riches, David W. H.
中科院分区：
文献类型：
--
作者：
Kostyk, Amanda G.;Dahl, Karen M.;Riches, David W. H.
慢性肺部炎症和感染是囊性纤维化（CF）发病率和死亡率的主要原因。虽然囊性纤维化跨膜传导调节因子（CFTR）突变对气道的影响仍存在争议，但一些研究组已证明CF气道表面液体中的Na+和Cl-与正常气道相比有所增加。我们研究了NaCl对巨噬细胞促炎趋化因子和细胞因子产生的影响。用增加量的NaCl刺激小鼠巨噬细胞诱导巨噬细胞炎性蛋白-2（MEP-2）和肿瘤坏死因子-α（TNF-α）产生。此外，在脂多糖（LPS）或TNF-α存在下，巨噬细胞与NaCl的共孵育协同增加MIP-2的产生。NaCl和NaCl加LPS反应都部分依赖于TNF-α的内源性产生和自分泌信号。为了研究CFTR在MEP-2产生中的作用，我们比较了野生型和Delta F508 CF小鼠巨噬细胞对NaCl和LPS的反应。来自两种菌株的巨噬细胞的反应是不可区分的。此外，CFTR mRNA在巨噬细胞中不表达。总之，这些发现表明，NaCl刺激MIP-2生产的巨噬细胞通过一种机制，是部分依赖于TNF-α，但独立于巨噬细胞CFTR表达。
Chronic pulmonary inflammation and infection are the leading causes of morbidity and mortality in cystic fibrosis (CF). While the effect of mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) on airways remains controversial, some groups have demonstrated increases in Na+ and Cl- in CF airway surface liquid compared to normal airways. We investigated the consequences of NaCl on pro-inflammatory chemokine and cytokine production by macrophages. Stimulation of mouse macrophages with increasing amounts of NaCl induced macrophage inflammatory protein-2 (MEP-2) and tumor necrosis factor-alpha (TNF-alpha) production. Further, co-incubation of macrophages with NaCl in the presence of either lipopolysaccharide (LPS) or TNF-alpha synergistically increased MIP-2 production. Both the NaCl and NaCl plus LPS responses were partially dependent on endogenous production and autocrine signaling by TNF-alpha. To investigate the role of CFTR in MEP-2 production, we compared the responses of wild-type and Delta F508 CF mouse macrophages; to NaCl and LPS. The responses of macrophages from both strains were indistinguishable. In addition, CFTR mRNA was not expressed in macrophages. Taken together, these findings suggest that NaCl stimulates MIP-2 production by macrophages through a mechanism that is partially dependent on TNF-alpha but independent of macrophage CFTR expression.