1994 Fiscal Year Final Research Report Summary
Interleukin-1 activates nuclear factor kappa-B and induces manganese superoxide dismutase in human hepatoma cells
| Project/Area Number |
05670442
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Yamagata University |
|---|
Principal Investigator |
TOGASHI Hitoshi The Second Department of Internal Medicine, Assistant Professor, 医学部, 講師 (60192209)
|
|---|
| Project Period (FY) |
1993 – 1994
|
| Keywords | primary cultured hepatcyte / human hepatoma cell / Interleukin-1 / Mn-SOD / NFkB |
|---|
| Research Abstract |
We examined the mechanism of Mn-SOD mRNA induction by inflammatory cytokines using primary rat hepatocytes and cultured human hepatoma cell line (Huh-6). Among inflammatory cytokines, Interleukin-1 (IL-1) induced the expression of Mn-SOD mRNA both in primary rat hepatocytes and Huh-6. Actinomycin D,an inhibitor of transcription, did not affect the IL-1-mediated induction of Mn-SOD mRNA.Cycloheximide, an inhibitor of protein synthesis, inhibited the IL-1-mediated induction of Mn-SOD mRNA.These results suggest that the increased expression of Mn-SOD mRNA is controlled at the transcriptional level and that it is due to synthesis of new protein. We examine the IL-1-mediated signal pathways leading to the induction of Mn-SOD mRNA using Huh-6. Phosphatidylcholine-phospholipase C might be a candidate responsible for the signal pathways. We next examined the DNA bindingactivity of C/EBP and NFkB after addition of IL-1 into the cultured medium.The activity of C/EBP did not change, but the activity of NFkB increased. TPCK,an inhibitor of NFkB,decreased the induction of Mn-SOD mRNA expression by IL-1.Furthermore, IL-1 enhanced the expression of p65 mRNA,which constitutes NFkB.We concluded that NFkB is essential for the increased expression of IL-1-mediated Mn-SOD mRNA.
|
