Decrease in circulating autotaxin by oral administration of prednisolone

• Published in: Clinica chimica acta 2013-01, Vol.415, p.74-80
• Main Authors: Sumida, Hayakazu, Nakamura, Kazuhiro, Yanagida, Keisuke, Ohkawa, Ryunosuke, Asano, Yoshihide, Kadono, Takafumi, Tamaki, Kunihiko, Igarashi, Koji, Aoki, Junken, Sato, Shinichi, Ishii, Satoshi, Shimizu, Takao, Yatomi, Yutaka
• Format: Article
• Language: English
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose Tissue - pathology; Administration, Oral; Animals; Autoimmune Diseases - blood; Autoimmune Diseases - drug therapy; Autoimmune Diseases - genetics; Autoimmune Diseases - pathology; Autotaxin (ATX); Biomarkers, Pharmacological - metabolism; Case-Control Studies; Female; Gene Expression - drug effects; Glucocorticoids - pharmacokinetics; Glucocorticoids - pharmacology; Humans; Immunoenzyme Techniques; Lysophosphatidic acid (LPA); Lysophosphatidylcholines - blood; Lysophospholipase D (LysoPLD); Lysophospholipid; Lysophospholipids - blood; Male; Mice; Mice, Inbred C57BL; Phosphoric Diester Hydrolases - blood; Phosphoric Diester Hydrolases - genetics; Phosphoric Diester Hydrolases - metabolism; Prednisolone (PSL); Prednisolone - pharmacokinetics; Prednisolone - pharmacology; Real-Time Polymerase Chain Reaction; Signal Transduction - drug effects; Tissue Culture Techniques
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2012.10.003

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. 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. 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. 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. ► ATX levels were measured in autoimmune disease patients before and after PSL therapy. ► ATX levels in serum of patients showed an inverse correlation with PSL dosage. ► During tapering of PSL dosage, ATX levels increased, independent of disease activity. ► Decreased ATX levels during PSL treatment correlated with decreased lysoPLD activity. ► PSL treatment decreased ATX mRNA levels in cultured murine adipose tissue.