2001 Fiscal Year Final Research Report Summary
The mechanism and its regulation of interleukin 1 biological activities
| Project/Area Number |
11470487
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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 |
Biological pharmacy
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| Research Institution | Faculty of Pharmaceutical Sciences, Nagoya City University |
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Principal Investigator |
ONOZAKI Kikuo Fac. Phar. Sci., Nagoya City Univ., Professor, 薬学部, 教授 (20101313)
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| Co-Investigator(Kenkyū-buntansha) |
TAKII Takemasa Fac. Phar. Sci., Nagoya City Univ., Assis. Professor, 薬学部, 助手 (80244573)
HAYASHI Hidetoshi Fac. Phar. Sci., Nagoya City Univ., Asso. Professor, 薬学部, 助教授 (80198853)
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| Project Period (FY) |
1999 – 2001
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| Keywords | IL-1 / IL-1 receptor / cytokine / ODC / antizyme / CHOP / melanoma / TLR |
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| Research Abstract |
IL-1 plays an important role in host reactions, including immunologic, inflammatory and hematologic reactions, and in regulation of cell proliferation and differentiation. In this study we attempted to clarify (A) the mechanism of IL-1 signaling leading to the inhibition of cell proliferation of human melanoma cells A375, (B) the regulatory mechanism of expression of IL-1 receptor (IL-1R) and its family in vitro and in vivo. The following points have been clarified.
(A)
1) It was suggested that IL-1 up-regulated the protein level of AZ, a reguratory factor of ornithine decarboxylase (ODC), at translational level, and IL-1 responsive region was present within the sequence of AZ mRNA.
2) CHOP contributed to the antiproliferative effect of IL-1 by augmenting IL-6 transcription
3) CHOP augmented the transcriptional activity of many factors, including NF-IL-6, AP-1, ISRE and NF-κB.
4) CHOP also appeared to stabilize the protein levels of other C/EBP family members.
5) TNF inhibited the proliferation of both IL-1 sensitive A375-6 cells and IL-1 resistant A375-R8 cells. The p38MAPK-dependent antiproliferative pathway of TNF was observed in these two cell clones however p38MAPK-independent apoptosis pathway was observed in only R8 cells. The anti-apoptosis factor with very short half life appeared to be present in A375-6 cells but not in R8 cells.
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Research Products
(6 results)
