Yonago Acta medica 2006;49:39-47
Suppression of LPS-induced Cyclooxygenase-2 (cox-2) Gene Expression in Mouse Macrophages by
Excretory/Secretory Products of Spirometra erinaceieuropaei Plerocercoids
Soji Fukumoto, Paramasari Dirgahayu*, Kozue Nunomura, Haruyo Matsuura and Kazumitsu Hirai
Division of Molecular Medical Zoology, Department of Microbiology and Pathology, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503 Japan; *Present address: Department of Parasitology, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia
The escape mechanism of parasites from inflammatory processes has been thought to be one of the most important tools for their survival in infected tissues. On the other hand, inducible cyclooxygenase-2 (cox-2) has been shown to play a major role in the process of inflammation. We investigated the effect of excretory/secretory (ES) products from the plerocercoids of Spirometra erinaceieuropaei on cox-2 gene expression in a murine macrophage cell line (RAW 264.7). Preincubation of the macrophages with the ES products inhibited LPS-induced cox-2 mRNA expression by 75% as well as its protein production. Dibutyryl cAMP enhances LPS-induced cox-2 mRNA expression. The ES products also inhibited this enhanced expression by 46%. Inhibition of p38 mitogen-activated protein kinase (MAPK) with SB203580 or that of extracellular signal-regulated protein kinase with PD98059 reduced LPS-induced cox-2 mRNA expression by 75% or 52%, respectively, along with its protein production. This evidence suggests that both MAPK pathways are crucial for full induction of cox-2 gene expression. One experiment using a transcriptional inhibitor, actinomycin-D, showed that the ES products destabilized LPS-induced cox-2 mRNA in RAW 264.7 macrophages. These results show that ES products from the plerocercoids of Spirometra erinaceieuropaei suppress LPS-induced cox-2 mRNA expression in murine RAW 264.7 macrophages, and may attenuate inflammation around the plerocercoids of S. erinaceieuropaei.
Key words: Spirometra erinaceieuropaei; lipopolysaccharide; macrophage; cyclooxygenase-2; mitogen-activated protein kinase