Woo Seong Ji, Lim Kyu, Park Su Yeon, Jung Mun Yhung, Lim Hye Song, Jeon Min-Gyu, Lee Sang-Il, Park Byung-Hyun
Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
Department of Biochemistry and Cancer Research Institute, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
J Nutr Biochem. 2015 Jul;26(7):713-20. doi: 10.1016/j.jnutbio.2015.01.011. Epub 2015 Mar 20.
It is suggested that n-3 polyunsaturated fatty acids (PUFAs) can be used in the preventive or therapeutic management of rheumatoid arthritis (RA); however, controversial results have been reported. Here, we examined the effects of a decrease in the n-6/n-3 PUFA ratio on RA using fat-1 transgenic mice. First, we tested whether fat-1 expression modulated signaling pathways in fibroblast-like synoviocytes (FLSs) stimulated with tumor necrosis factor α (TNF-α). TNF-α activated p38 mitogen-activated protein kinase and increased phosphorylation of the signal transducer and activator of transcription 3 in wild type (WT) FLSs but not in fat-1 FLSs. Arthritis was induced by injection of K/BxN serum. Based on clinical scores, ankle thickness and pathological severity, we showed that WT mice developed clinically overt arthritis, whereas fat-1 mice showed attenuated arthritis. Moreover, fat-1 mice exhibited down-regulated local and systemic levels of inflammatory cytokines. Lastly, bone marrow-derived macrophages (BMMs) of WT mice differentiated into tartrate-resistant acid phosphatase-positive multinucleated osteoclasts, whereas the osteoclastogenenic process was suppressed in BMMs of fat-1 mice. The endogenous conversion of n-6 to n-3 PUFAs via fat-1 plays a key role in attenuation of RA; therefore, dietary supplementation of n-3 PUFAs may have therapeutic potential for the management of RA.
有人提出，n-3多不饱和脂肪酸（PUFAs）可用于类风湿性关节炎（RA）的预防或治疗；然而，已有相互矛盾的结果报道。在此，我们使用fat-1转基因小鼠研究了n-6/n-3 PUFA比值降低对RA的影响。首先，我们测试了fat-1的表达是否调节肿瘤坏死因子α（TNF-α）刺激的成纤维样滑膜细胞（FLSs）中的信号通路。TNF-α激活了野生型（WT）FLSs中的p38丝裂原活化蛋白激酶，并增加了信号转导和转录激活因子3的磷酸化，但在fat-1 FLSs中未出现这种情况。通过注射K/BxN血清诱导关节炎。基于临床评分、踝关节厚度和病理严重程度，我们发现WT小鼠出现了临床上明显的关节炎，而fat-1小鼠的关节炎症状减轻。此外，fat-1小鼠的局部和全身炎症细胞因子水平下调。最后，WT小鼠的骨髓来源巨噬细胞（BMMs）分化为抗酒石酸酸性磷酸酶阳性的多核破骨细胞，而fat-1小鼠的BMMs中的破骨细胞生成过程受到抑制。通过fat-1将n-6内源性转化为n-3 PUFAs在减轻RA中起关键作用；因此，饮食中补充n-3 PUFAs可能对RA的治疗具有潜在作用。
