2003 Fiscal Year Final Research Report Summary
Identification of cytokines secreted by Niemann-Pick cells
| Project/Area Number |
14570077
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Tottori University |
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Principal Investigator |
NINOMIYA Haruaki Tottori University, Department of Neurobiology, Associate Professor, 医学部, 助教授 (80212124)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Niemann-Pick / cytokine / cholesterol |
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| Research Abstract |
cDNA microarray analyses revealed increased mRNA levels of interferon-stimulated response element (ISRE)-driven genes such as MxA (myxovirus resistance A) and 2'-5' oligoadenylate synthetase in Niemann-pick disease type C (NPC) human skin fibroblasts. Of the proteins located upstream to ISRE, levels of STArs (signal transducers and activators of transcription) were increased in these cells. Similar increases in STAT levels were detected in extracts from NPC1-deficient CHO cells and NPC mouse brain and liver. In NPC mouse brain sections, reactive glial cells contained high STAT-3 immunoreactivity. Conditioned media from NPC fibroblasts contained high levels of proinflammatory cytokines interferon-β, IL-6, IL-8 and had activities to induce luciferase expression driven by ISRE, STAT-3 as well as GAS, and also to induce MxA expression in control cells. The activities to induce expression of ISRE-driven luciferase and MxA were absorbed by a neutralizing antibody against interferon-β whereas activities to induce expression of STAT-3-or GAS-driven luciferase were absorbed by a neutralizing antibody against IL-6. These results suggest constitutive activation of STAT signaling due to proinflammatory cytokines both in cultured NPC cells and mouse tissues.
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Research Products
(17 results)
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[Publications] Hou L., Sugimoto Y., Ohsaki Y., Ninomiya H., Oka A., Taniguchi M., Ida H., Eto Y., Ogawa S., Matsuzaki Y., Sawa M., Inoue T., Higaki K., Nanba E., Ohno K., Suzuki Y.: "N-Octyl-β-valienamine up-regulates activity of F213I mutant β-glucosidase in cultured cells : a potential chemical chaperone therapy for Gaucher disease."Biochim.Biophys.Acta. (in press).
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[Publications] Wakutani Y., Watanabe K., Adachi Y., Wada-Isoe K., Urakami K., Ninomiya H., Ohno K., Saido T.C., Hashimoto T., Iwatsubo T., Nakashima K.: "Novel amyloid precursor protein gene missense mutation (D678N) in familial Alzheimer's disease."J.Neurol.Neurosurg.Psychiat. (in press). (2004)
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[Publications] Pipo J.R., Feng J.H., Yamamoto T., Ohsaki Y., Nanba E., Taujino S., Sakuragawa N., Martiniuk F., Ninomiya H., Oka A., Ohno K.: "New GAA mutations in Japanese patients with GSDII (pompe disease)."Pediatr Neurol.. 29. 284-287 (2003)
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