Carbon monoxide-releasing molecule, CORM-3, modulates alveolar macrophage M1/M2 phenotype in vitro
Carbon monoxide-releasing molecule, CORM-3, modulates alveolar macrophage M1/M2 phenotype in vitro
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一氧化碳释放分子 CORM-3 在体外调节肺泡巨噬细胞 M1/M2 表型
DOI：
10.1007/s10787-017-0371-y
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发表时间：
2017
影响因子：
5.8
通讯作者：
Nishiyama Noritoshi
中科院分区：
文献类型：
--
作者：
Yamamoto-Oka Hiroko;Mizuguchi Shinjiro;Toda Michihito;Minamiyama Yukiko;Takemura Shigekazu;Shibata Toshihiko;Cepinskas Gediminas;Nishiyama Noritoshi
肺泡巨噬细胞是促进和消除肺部炎症的关键因素，分为促炎（M1）和抗炎（M2）表型。 M1/M2 平衡的变化已在多种肺部疾病中得到报道，并且是治疗干预的目标。本研究的目的是评估水溶性一氧化碳释放分子 3 (CORM-3) 对肺泡巨噬细胞 M1/M2 表型的调节。用 LPS (5 ng/ml)/IFN-γ (10 U/ml) 或 IL-4 (10 ng/ml)/IL-13 (10 ng/ml) 刺激培养物中的大鼠肺泡巨噬细胞 (AM) (NR8383)，分别诱导 M1 和 M2 表型。在不存在或存在 CORM-3 (0.15 mM) 处理的情况下，1、3、6 或 24 小时后，通过蛋白质印迹评估 M1 表型标记物、iNOS 和 TNF-α 以及 M2 表型标记物、CD206 和 Ym-1 的表达。非活性 CORM-3 (iCORM-3) 用作对照。用 CORM-3 治疗初始（未刺激）AM 促进了 M2 表型的进展，CD206（1 小时；1.8 倍）和 Ym-1（3 小时；1.9 倍）表达分别增加证明了这一点。令人惊讶的是，CORM-3 刺激 AM 6 小时后评估，CORM-3 处理还上调了 iNOS 蛋白的表达（2.6 倍）。相反，CORM-3有效降低LPS/IFN-γ诱导的iNOS蛋白表达（0.6倍）；然而，它对TNF-α的表达没有影响。最后，CORM-3 急剧（1-3 小时）上调 IL-4-/IL-13 处理（M2 刺激）巨噬细胞中的 CD206（1.4 倍）和 Ym-1（1.6 倍）水平。这些发现表明，CORM-3 在体外调节巨噬细胞 M1 和 M2 表型，持续抑制 M1 极化巨噬细胞中的 iNOS 表达，并短暂（早期）上调 M2 极化巨噬细胞中的 CD206 和 Ym-1 蛋白。
Alveolar macrophages are key contributors to both the promotion and resolution of inflammation in the lung and are categorized into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. The change in M1/M2 balance has been reported in various pulmonary diseases and is a target for therapeutic intervention. The aim of this study was to assess the modulation of M1/M2 phenotype in alveolar macrophages by water-soluble carbon monoxide-releasing molecule-3 (CORM-3). Rat alveolar macrophages (AM) (NR8383) in culture were stimulated with LPS (5 ng/ml)/IFN-γ (10 U/ml) or IL-4 (10 ng/ml)/IL-13 (10 ng/ml) to induce M1 and M2 phenotypes, respectively. Expression of M1 phenotype markers, iNOS and TNF-α, and M2 phenotype markers, CD206 and Ym-1, was assessed by western blotting after 1, 3, 6, or 24 h in the absence or presence of CORM-3 (0.15 mM) treatment. Inactive CORM-3 (iCORM-3) was used as a control. Treatment of naïve (unstimulated) AM with CORM-3 promoted progression of the M2 phenotype as evidenced by the increased expression of CD206 (at 1 h; 1.8-fold) and Ym-1 (at 3 h; 1.9-fold), respectively. Surprisingly, CORM-3 treatment also upregulated the expression of iNOS protein as assessed 6 h following stimulation of AM with CORM-3 (2.6-fold). On the contrary, CORM-3 effectively reduced LPS/IFN-γ-induced expression of iNOS protein (0.6-fold); however, it had no effect on TNF-α expression. Finally, CORM-3 acutely (1–3 h) upregulated CD206 (1.4-fold) and Ym-1 (1.6-fold) levels in IL-4-/IL-13-treated (M2-stimulus) macrophages. These findings indicate that CORM-3 modulates macrophage M1 and M2 phenotypes in vitro with respect to continuous suppression of iNOS expression in M1-polarized macrophages and transient (early-phase) upregulation of CD206 and Ym-1 proteins in M2-polarized macrophages.
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DOI：
10.1165/rcmb.4816
发表时间：
2002-12-01
影响因子：
6.4
作者：
Sarady, JK;Otterbein, SL;Choi, AMK
通讯作者：
Choi, AMK
影响因子：
4.6
作者：
Boorsma CE;Draijer C;Melgert BN
通讯作者：
Melgert BN
全身应用 CO 释放分子 3 可减轻室综合征引起的微血管功能障碍的严重程度
DOI：
--
发表时间：
2014
期刊：
Journal of Orthopaedics and Trauma
影响因子：
--
作者：
A. Lawendy;A. Bihari;D. Sanders;R. Potter;G. Cepinskas
通讯作者：
G. Cepinskas
影响因子：
4.8
作者：
Martínez-Pomares, L;Mahoney, JA;Gordon, S
通讯作者：
Gordon, S