Decrease in circulating autotaxin by oral administration of prednisolone

Decrease in circulating autotaxin by oral administration of prednisolone
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DOI:
10.1016/j.cca.2012.10.003
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发表时间:
2013-01-16
影响因子:
5
通讯作者:
Yatomi, Yutaka
Yatomi, Yutaka
中科院分区:
医学3区
文献类型:
--
作者:
Sumida, Hayakazu;Nakamura, Kazuhiro;Yatomi, Yutaka

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背景资料:主要由脂肪组织分泌的自分泌运动因子(ATX)作为溶血磷脂酶D(lysoPLD)起作用以将溶血磷脂酰胆碱(LPC)水解成溶血磷脂酸(LPA)。ATX LPA信号转导牵连在广泛的生理和病理生理过程,包括immune response.Methods:本研究测量血清ATX抗原水平的各种自身免疫性疾病患者使用最近开发的自动化酶免疫分析。此外,通过测量从底物LPC释放的胆碱来评估血清lysoPLD活性。此外,泼尼松龙(PSL)对ATX mRNA表达的影响进行了评估,使用培养的脂肪组织从小鼠。结果:降低血清ATX抗原水平后,观察开始与PSL治疗。在PSL剂量递减期间,降低的水平以剂量依赖性方式恢复,而未加重疾病活动。此外,降低ATX mRNA的表达在PSL处理培养的小鼠脂肪组织表明,PSL对血清ATX的影响可能导致脂肪组织ATX expression.Conclusions的变化:我们的研究结果表明,血清ATX抗原水平的测量可能是临床上有用的类固醇治疗效果和药物依从性的评估与类固醇。此外,我们的研究结果提供了许多新的见解循环ATX的生物合成,生理功能,病理作用和临床意义。(c)2012爱思唯尔有限公司版权所有。
Background: Autotaxin (ATX), secreted mainly from adipose tissue, functions as a lysophospholipase D (lysoPLD) to hydrolyze lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). ATX LPA signaling is implicated in a wide range of physiological and pathophysiological processes including immune response.Methods: The present study measured serum ATX antigen levels in patients with various autoimmune diseases using a recently developed automated enzyme immunoassay. In addition, serum lysoPLD activity was assessed by measuring choline liberation from the substrate LPC. Moreover, the effect of prednisolone (PSL) on mRNA expression of ATX was evaluated using cultured adipose tissue from mice.Results: Decreased serum ATX antigen levels were observed after the initiation of treatment with PSL. The decreased levels recovered during tapering of PSL dose in a dose-dependent manner without exacerbation of disease activity. Moreover, decreased ATX mRNA expression in PSL-treated cultured murine adipose tissue suggested that the effect of PSL on serum ATX may have resulted from changes in adipose tissue ATX expression.Conclusions: Our results suggest that measurement of serum ATX antigen level may be clinically useful for the assessment of steroid treatment effect and drug compliance with steroids. Furthermore, our findings provide many novel insights into the biosynthesis, physiological functions, pathological roles, and clinical significance of circulating ATX. (c) 2012 Elsevier B.V. All rights reserved.