Background

As a partial μ-opioid receptor agonist with long half-life time, buprenorphine has been widely used to relieve chronic cancer and nonmalignant pain. The maintenance of chronic pain involves inflammation; however whether buprenorphine has anti-inflammation property remains unclear.

Methods

Macrophages, the immune cells that initiate and maintain inflammation, were isolated from human umbilical cord blood, and were polarized into M1 or M2 macrophages with IFN-γ in the presence of lipopolysaccharide (LPS) or IL-4, respectively. Quantitative PCR, ELISA,Western blotting analysis, and chromatin immunoprecipitation assays were employed to characterize M1 and M2 macrophages.

Results

1) Buprenorphine did not change not only the apoptosis, survival, andmorphology of resting macrophages, but also the antigen-presenting function of macrophages. 2) Buprenorphine inhibited the levels of mRNA and protein of several cytokines in M1 macrophages, and enhanced the expression of Ym1 and Fizz1 in M2 macrophages. 3) Buprenorphine did not affect the modulation of NF-κB and MAPK cascades by LPS in M1 macrophages. 4) Buprenorphine inhibited the expression of IRF5 and reduced binding of DNA to IRF5.

Conclusion

Buprenorphine may downregulate IRF5 pathway and limit M1 macrophage phenotype. These effects may contribute to its therapeutic benefit for chronic neuropathic pain.

中文翻译：

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丁丙诺啡对人脐带血中的M1和M2极化巨噬细胞有不同的影响。

背景

作为半衰期长的部分μ阿片类受体激动剂，丁丙诺啡已被广泛用于缓解慢性癌症和非恶性疼痛。慢性疼痛的维持涉及炎症。但是尚不清楚丁丙诺啡是否具有抗炎作用。

方法

巨噬细胞是引发和维持炎症的免疫细胞，是从人脐带血中分离出来的，并在存在脂多糖（LPS）或IL-4的情况下被IFN-γ极化成M1或M2巨噬细胞。定量PCR，ELISA，Western印迹分析和染色质免疫沉淀测定法用于表征M1和M2巨噬细胞。

结果

1）丁丙诺啡不仅不改变静止巨噬细胞的凋亡，存活和形态，而且不改变巨噬细胞的抗原呈递功能。2）丁丙诺啡抑制M1巨噬细胞中几种细胞因子的mRNA和蛋白水平，并增强M2巨噬细胞中Ym1和Fizz1的表达。3）丁丙诺啡不影响M1巨噬细胞中LPS对NF-κB和MAPK级联的调节。4）丁丙诺啡抑制IRF5的表达并减少DNA与IRF5的结合。

结论

丁丙诺啡可能下调IRF5通路并限制M1巨噬细胞表型。这些作用可能有助于其对慢性神经性疼痛的治疗作用。