Laboratory of Histocompatibility and Cryopresevation, Rio de Janeiro State University, Rio de Janeiro, Brazil.
NuMeCan Institute (Nutrition, Metabolism and Cancer), INSERM, INRAE, CHU Rennes, Hôpital Pontchaillou, Univ Rennes, 35033, Rennes Cedex, France.
Sci Rep. 2020 Jul 30;10(1):12796. doi: 10.1038/s41598-020-68753-1.
Cigarette smoke exposure (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD). Macrophages have an important role in COPD because they release pro-inflammatory and anti-inflammatory cytokines. The present study's we investigate the functional changes in macrophages and monocytes exposed to cigarette smoke extract (CSE). Herein, using human monocyte-derived macrophages (MDMs) from healthy donors and we found that CSE was not associated with significant changes in the production of pro inflammatory cytokines by MDMs. In contrast, exposure to CSE suppressed the production of IL-6 and Gro-a/CXCL1 by LPS-stimulated-MDMs, but had an additive effect on the release of IL-8/CXCL8 and MCP1/CCL2. However, CSE exposure was associated with greater production, TARC/CCL-17 and CCL22/MDC. Moreover, MDMs displayed a lower uptake capacity after CSE exposure. We identify, for what is to our knowledge the first time that monocytes from patients with COPD produced less IL-8/CXCL8 and Gro-α/CXCL1 after LPS stimulation and produced higher levels of TARC/CCL17 and MDC/CCL-22 after IL-4 stimulation. Our present results highlighted a skewed immune response, with an imbalance in M1 vs. M2 cytokine production. In conclusion, exposure to CS has contrasting, multifaceted effects on macrophages and monocytes. Our data may provide a better understanding of the mechanisms underlying COPD.
吸烟暴露（CS）是慢性阻塞性肺疾病（COPD）的主要危险因素。巨噬细胞在 COPD 中具有重要作用，因为它们释放促炎和抗炎细胞因子。本研究我们调查了暴露于香烟烟雾提取物（CSE）的巨噬细胞和单核细胞的功能变化。在此，我们使用来自健康供体的人单核细胞衍生的巨噬细胞（MDM），发现 CSE 与 MDM 产生促炎细胞因子的变化无关。相比之下，CSE 暴露抑制 LPS 刺激的-MDMs 产生 IL-6 和 Gro-a/CXCL1，但对 IL-8/CXCL8 和 MCP1/CCL2 的释放具有附加作用。然而，CSE 暴露与更高的 TARC/CCL-17 和 CCL22/MDC 产生有关。此外，CSE 暴露后 MDMs 的摄取能力降低。我们首次发现，与健康对照组相比，COPD 患者的单核细胞在 LPS 刺激后产生的 IL-8/CXCL8 和 Gro-α/CXCL1 减少，在 IL-4 刺激后产生的 TARC/CCL17 和 MDC/CCL-22 增加。我们目前的结果强调了免疫反应的倾斜，M1 与 M2 细胞因子产生之间存在不平衡。总之，CS 暴露对巨噬细胞和单核细胞具有相反的、多方面的影响。我们的数据可能提供了对 COPD 潜在机制的更好理解。
