Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis
Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis
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DOI：
10.1007/s00011-012-0489-8
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发表时间：
2012-09-01
影响因子：
6.7
通讯作者：
Weylandt, Karsten H.
中科院分区：
文献类型：
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作者：
Chiu, Cheng-Ying;Gomolka, Beate;Weylandt, Karsten H.
来源于ω-3和ω-6脂肪酸的酶促氧化脂质产物在炎症抑制中起重要作用。本研究检测了n-6二十二碳五烯酸衍生的（17 S）-羟基-二十二碳五烯酸的抗炎作用（17-HDPAn-6）和（10，17 S）-二羟基-二十二碳五烯酸（10，17-HDPAn-6）以及n-3二十二碳六烯酸衍生的17（R/S）-羟基-二十二碳六烯酸（17-HDHA）。采用吞噬实验和实时荧光定量PCR检测了17-HDPAn-6和17-HDHA对小鼠巨噬细胞系RAW 264.7活性和M1/M2极化的影响。为了评估体内抗炎作用，在用17-HDPAn-6、10，17-HDPAn-6、17-HDHA或NaCl处理的小鼠中诱导葡聚糖硫酸钠（DSS）结肠炎。17-HDPAn-6和17-HDHA在体外增加巨噬细胞的吞噬作用，并促进向抗炎M2表型的极化，同时降低TNF-α的基因表达。α和诱导型一氧化氮合酶以及趋化因子IL-1受体拮抗剂和A型清道夫受体的表达增加。17-HDPAn-6、10，17-HDPAn-6或17-HDHA腹腔内治疗可缓解DSS结肠炎，并显着改善体重减轻、结肠上皮损伤和巨噬细胞浸润。这些结果表明DPAn-6衍生的17-HDPAn-6和10，17-HDPAn-6以及DHA衍生的17-HDHA具有炎症抑制和消退作用，促进可用于治疗炎性病症如炎性肠病的效果。
Enzymatically oxygenated lipid products derived from omega-3 and omega-6 fatty acids play an important role in inflammation dampening. This study examined the anti-inflammatory effects of n-6 docosapentaenoic acid-derived (17S)-hydroxy-docosapentaenoic acid (17-HDPAn-6) and (10,17S)-dihydroxy-docosapentaenoic acid (10,17-HDPAn-6) as well as n-3 docosahexaenoic acid-derived 17(R/S)-hydroxy-docosahexaenoic acid (17-HDHA).The effects of 17-HDPAn-6, 10,17-HDPAn-6 or 17-HDHA on activity and M1/M2 polarization of murine macrophage cell line RAW 264.7 were examined by phagocytosis assay and real-time PCR. To assess anti-inflammatory effects in vivo, dextran sodium sulfate (DSS) colitis was induced in mice treated with 17-HDPAn-6, 10,17-HDPAn-6, 17-HDHA or NaCl.Our results show that 17-HDPAn-6, 10,17-HDPAn-6 and 17-HDHA increase phagocytosis in macrophages in vitro and promote polarization towards the anti-inflammatory M2 phenotype with decreased gene expression of TNF-alpha and inducible Nitric oxide synthase and increased expression of the chemokine IL-1 receptor antagonist and the Scavenger receptor Type A. Intraperitoneal treatment with 17-HDPAn-6, 10,17-HDPAn-6, or 17-HDHA alleviated DSS-colitis and significantly improved body weight loss, colon epithelial damage, and macrophage infiltration.These results suggest that DPAn-6-derived 17-HDPAn-6 and 10,17-HDPAn-6 as well as the DHA-derived 17-HDHA have inflammation-dampening and resolution-promoting effects that could be used to treat inflammatory conditions such as inflammatory bowel disease.