Kim Bo Sook, Spinner Daryl S, Kascsak Richard J, Park Seung Yong, Cho In Soo, Schuller-Levis Georgia, Park Eunkyue
Seoul Grand Park Zoo,Gwacheon, Gyunggi-do 427-702, Korea.
J Drugs Dermatol. 2013 May;12(5):551-7.
Taurine plays an important role in brain and retinal development, and has an antiinflammatory and antioxidant function. Taurine chloramine (Tau-Cl) is produced in polymorphonuclear leukocytes via the myeloperoxidase/halide system. We previously demonstrated that Tau-Cl inhibits the production of nitric oxide (NO) and TNF-α in human and murine macrophages activated with IFN-γ in combination with individual Toll-like receptor (TLR) ligands including those for TLR2 and/or TLR4. In the current study, we further explored the effects of Tau-Cl in RAW 264.7 cells stimulated with the TLR9 ligand CpG oligodeoxynucleotide (ODN). Specifically, we examined the effect of CpG ODN plus IFN-γ on the production of NO and TNF-α, and the effect of Tau-Cl on this process. Our findings show that CpG ODN plus IFN-γ-activated RAW 264.7 cells secrete high levels of NO and TNF-α, and that Tau-Cl (0.8 mM) inhibits this effect in a dose-dependent manner, more potently inhibiting the production of NO (99% inhibition) than that of TNF-α (48% inhibition). Nitric oxide synthase (iNOS) protein was also induced by CpG ODN plus IFN-γ, and was also inhibited by Tau-Cl. Furthermore, while CpG ODN plus IFN-γ induced TNF-α and iNOS mRNAs, Tau-Cl transiently suppressed this effect. Taurine itself had no effects on any of these processes. Our findings in a macrophage cell line demonstrate that Tau-Cl inhibits proinflammatory mediators resulting from TLR9 activation, and have implications for the utility of Tau-Cl in scenarios where such activation is deleterious such as in autoimmune conditions or infections in which overwhelming inflammation may occur. CpG ODNs and Tau-Cl both have potential for topical treatment of autoimmune conditions, including psoriasis, vitiligo, and alopecia areata. As CpG ODNs may, under some conditions, up-regulate Tregs, addition of Tau-Cl to CpG ODN topical formulations has potential for improving cancer immunotherapy.
牛磺酸在大脑和视网膜发育中发挥着重要作用，并具有抗炎和抗氧化功能。氯胺牛磺酸（Tau-Cl）通过髓过氧化物酶/卤化物系统在多形核白细胞中产生。我们之前证明，Tau-Cl可抑制经γ干扰素联合包括Toll样受体2（TLR2）和/或Toll样受体4（TLR4）配体在内的单个Toll样受体（TLR）配体激活的人和小鼠巨噬细胞中一氧化氮（NO）和肿瘤坏死因子-α（TNF-α）的产生。在本研究中，我们进一步探讨了Tau-Cl对用TLR9配体CpG寡脱氧核苷酸（ODN）刺激的RAW 264.7细胞的影响。具体而言，我们研究了CpG ODN加γ干扰素对NO和TNF-α产生的影响，以及Tau-Cl对这一过程的影响。我们的研究结果表明，CpG ODN加γ干扰素激活的RAW 264.7细胞分泌高水平的NO和TNF-α，而Tau-Cl（0.8 mM）以剂量依赖性方式抑制这种作用，对NO产生的抑制作用（99%抑制）比TNF-α（48%抑制）更强。CpG ODN加γ干扰素还诱导了一氧化氮合酶（iNOS）蛋白的表达，而Tau-Cl也对其产生了抑制作用。此外，虽然CpG ODN加γ干扰素诱导了TNF-α和iNOS的信使核糖核酸（mRNA），但Tau-Cl可短暂抑制这种作用。牛磺酸本身对这些过程均无影响。我们在巨噬细胞系中的研究结果表明，Tau-Cl可抑制由TLR9激活产生的促炎介质，这对于Tau-Cl在诸如自身免疫性疾病或可能发生过度炎症的感染等TLR9激活有害的情况下的应用具有重要意义。CpG ODN和Tau-Cl在包括银屑病、白癜风和斑秃在内的自身免疫性疾病的局部治疗中均具有潜力。由于CpG ODN在某些情况下可能上调调节性T细胞（Tregs），在CpG ODN局部制剂中添加Tau-Cl有可能改善癌症免疫治疗。
