| Project/Area Number |
16390127
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including Sanitary zoology)
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
ARIZONO Naoki Kyoto Prefectural University of Medicine, Graduate School of Medicine, Professor, 医学研究科, 教授 (10079725)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Minoru Kyoto Prefectural University of Medicine, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (70106392)
UCHIKAWA Ryuichi Kyoto Prefectural University of Medicine, Graduate School of Medicine, Research Associate, 医学研究科, 助手 (80145466)
TEGOSHI Tatsuya Kyoto Prefectural University of Medicine Graduate School of Medicine, Graduate School of Medicine, Research Associate, 医学研究科, 助手 (40254370)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Keywords | nematode / mucus / intestine / sialyltransferase / sulfotransferase / T cell / IL-4 / Nippostrongylus / HSP / MUC / TNF / マスト細胞 / マウス |
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| Research Abstract |
Intestinal nematode infections induce marked goblet cell hyperplasia and mucus secretion, but its role and regulation mechanisms have not been fully understood. The present study aimed at elucidation of the regulation mechanisms of the epithelial mucus production after nematode infections. The gene expression of rat intestinal epithelial cells during infection with the nematode Nippostrongylus brasiliensis studied by reverse transcription (RT)-realtime PCR showed that mucin core peptide (MUC) 2, sialyltransferase (Siat) 4c and trefoil factor family (TFF) 3 were upregulated as early as 2-4 days post-infection, suggesting that they are associated with an early innate protective response. Seven days after infection and thereafter, when nematodes reached the sexual maturity, MUC3, MUC4, resistin-like molecule beta (Relm-beta) and 30-sulfotransferase (3ST)1 genes exhibited marked upregulation. Similar alterations of glycosylation-related gene expression were also observed in mast-cell-deficient Ws/Ws rats, while in athymic rnu/rnu rats, expression levels of Relm-beta, Siat4c and 3ST1 were significantly lower than in +/+ rats. In vitro studies using the rat intestinal cell-line, IEC-6, showed that Siat4c and 3ST1 gene expression was significantly upregulated in response to the administration of IL-4 and/or IL-13, indicating that the expression of the sialyl-and sulfo-transferases is regulated by Th2 cytokines. Similarly, in immune-deficient scid mice infected with the nematode Heligmosomoides polygyrus, Siat4c gene expression was significantly lower than in +/+ mice. Overall, these results suggested that Th2 cytokines have an important role in the modulation of terminal sugar chains of mucin and membrane glycoprotein via the upregulation of Siat4c and 3ST1 expression in intestinal epithelial cells.
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