1999 Fiscal Year Final Research Report Summary
Molecular mechanisms of IL-8 gene expression by the immediate early gene products of cytomegelovirus
| Project/Area Number |
09670320
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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 |
Virology
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| Research Institution | Kagoshima University (1999)
Kanazawa Medical University (1997-1998) |
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Principal Investigator |
MURAYAMA Tsugiya Faculty of Medicine, Kagoshima University, Associate Professor, 医学部, 助教授 (60159184)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Cytomegalovirus / IL-8 / U373MG cell / luciferase reporter gene assay / NF-kB / AP-1 |
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| Research Abstract |
We previously observed that human cytomegalovires (CMV) infection induced a massive production of an interleukin-8 (IL-8) in a THP-1 cell. Hence, we examined the effect of CMV immediate early (IE) gene products on IL-8 production by the human astrocytoma cell line, U373MG. Transiently or stably transfection with CMV IE1 but not with CMV IE2 gene significantly augmented IL-8 protein secretion and IL-8 mRNA expression, compared with transfection with a control vector. Moreover, luciferase activity was enhanced in U373MG cells that were co-transfected with CMV IE1 and a chimeric firefly luciferase reporter genes driven by the transcriptional regulatory region of the human IL-8 gene. Furthermore, IE1 gene-mediated enhancement of luciferase activities was abolished by the introduction of the mutation into AP-1 or NF-kB factor binding elements in the regulatory region of the IL-8 gene, as previously observed on CMV infected cells. Finally, Western blotting as well as an immunohistochemical analysis demonstrated that CMV IE1 gene products increased the amount of p65 of NF-kB complexes translocated into the nuclei. Collectively, CMV IE1 gene expression may be sufficient to activates AP-1 and NF-kB, resulting in IL-8 gene expressions.
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