Alveolar macrophage cathelicidin deficiency in severe sarcoidosis.
Alveolar macrophage cathelicidin deficiency in severe sarcoidosis.
复制标题
DOI：
10.1159/000339149
复制
发表时间：
2012
影响因子：
5.3
通讯作者：
Thomassen MJ
中科院分区：
文献类型：
--
作者：
Barna BP;Culver DA;Kanchwala A;Singh RJ;Huizar I;Abraham S;Malur A;Marshall I;Kavuru MS;Thomassen MJ
功能失调的免疫反应是结节病的特征，但凯萨林菌素（一种有效的免疫调节和抗微生物分子）在临床疾病活动中的地位尚未确定。肺泡巨噬细胞cathelicidin的表达是在活检证实的结节病患者中确定的，临床分类为“严重”（需要全身治疗）或“非严重”（从不需要治疗）。通过定量PCR分析结节病和健康对照支气管肺泡灌洗（BAL）细胞中凯萨林菌素、维生素D受体（VDR）和VDR共激活剂、类固醇受体共激活剂-3（SRC 3）的mRNA表达。用免疫细胞化学法检测Cathelicidin衍生肽LL-37的表达。对血清骨化二醇[25（OH）vitD 2]（vitD 2）和骨化三醇[1，25（OH）2 vitD 3]（vitD 3）进行定量。结果表明，与对照组相比，在重度而非非重度结节病中，组织蛋白酶抑制素和SRC 3的BAL细胞表达减少。尽管两组的vitD 2水平均低于推荐水平（30 ng/ml），但重症和非重症患者的生物活性vitD 3血清水平均在控制范围内。在体外研究结节病和对照肺泡巨噬细胞，以确定cathelicidin对vitD 3和肿瘤坏死因子-α（TNFα）的反应，TNF α是一种在活动性结节病中升高的vitD 3拮抗剂。vitD 3刺激肺泡巨噬细胞cathelicidin，但TNFα抑制cathelicidin，TNFα也抑制SRC 3。研究结果表明，TNFα介导的SRC 3抑制导致严重结节病患者肺泡巨噬细胞cathelicidin缺乏，尽管vitD 3水平正常。cathelicidin是一种免疫细胞和促炎细胞因子的多功能调节剂，缺乏cathelicidin可能会阻碍严重结节病肺部炎症的消退。
Dysfunctional immune responses characterize sarcoidosis but the status of cathelicidin, a potent immunoregulatory and anti-microbial molecule has not been established in clinical disease activity. Alveolar macrophage cathelicidin expression was determined in biopsy-proven sarcoidosis patients classified clinically as “severe” (requiring systemic treatment) or “non-severe” (never requiring treatment). Sarcoidosis and healthy control bronchoalveolar lavage (BAL) cells were analyzed for mRNA expression of cathelicidin, vitamin D receptor (VDR), and the VDR co-activator, steroid receptor co-activator-3 (SRC3) by quantitative PCR. Cathelicidin-derived peptide LL-37 was determined by immunocytochemistry. Serum calcidiol [25(OH)vitD2] (vitD2) and calcitriol [1,25(OH)2vitD3] (vitD3) were quantified. Results indicated reduced BAL cell expression of cathelicidin and SRC3 in severe but not non-severe sarcoidosis compared to controls. Serum levels of biologically active vitD3 in both severe and non-severe patients were within control range even though vitD2 levels in both groups were below recommended level (30ng/ml). Sarcoidosis and control alveolar macrophages were studied in vitro to determine cathelicidin responses to vitD3 and tumor necrosis factor-alpha (TNFα), a vitD3 antagonist elevated in active sarcoidosis. Alveolar macrophage cathelicidin was stimulated by vitD3 but repressed by TNFα which also repressed SRC3. Findings suggest that TNFα-mediated repression of SRC3 contributes to alveolar macrophage cathelicidin deficiency in severe sarcoidosis despite healthy vitD3 levels. Deficiency of cathelicidin, a multifunctional regulator of immune cells and pro-inflammatory cytokines, may impede resolution of inflammation in severe sarcoidosis lung.
登录
查看更多内容
影响因子：
4.4
作者：
Nijnik, Anastasia;Pistolic, Jelena;Hancock, Robert E. W.
通讯作者：
Hancock, Robert E. W.
影响因子：
5.8
作者：
Dusso, AS;Kamimura, S;Slatopolsky, E
通讯作者：
Slatopolsky, E
DOI：
10.1152/ajplung.00216.2003
发表时间：
2003-11-01
影响因子：
4.9
作者：
Bonfield, TL;Raychaudhuri, B;Thomassen, MJ
通讯作者：
Thomassen, MJ
影响因子：
4.1
作者：
Hewison M
通讯作者：
Hewison M
DOI：
10.1086/596314
发表时间：
2009-02-15
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Gombart AF;Bhan I;Borregaard N;Tamez H;Camargo CA Jr;Koeffler HP;Thadhani R
通讯作者：
Thadhani R