2010 Fiscal Year Final Research Report
The effect of Fractalkine in the progression of chronic pancreatitis
| Project/Area Number |
20590808
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
ITO Tetsuhide Kyushu University, 大学病院, 講師 (50253448)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IGARASHI Hisato 九州大学, 大学病院, 助教 (60467941)
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Keywords | 慢性膵炎 / フラクタルカイン / 膵線維化 / 膵星細胞 / ケモカイン / プロテインカイネースC |
|---|
| Research Abstract |
Chronic pancreatitis, an irreversible inflammatory disease of the pancreas, is characterized by chronic inflammatory cell infiltration, acinar cell degeneration, and development of fibrosis, which lead to impairment of pancreatic exocrine and endocrine function. Recently, a role for fractalkine/CX3CR1-mediated inflammation has been demonstrated in several initial inflammatory disorders. Therefore, at first, we elucidated the elevation of serum Fractalkine level in patients with chronic pancreatitis, especially in early-stage. Next, using DBTC chronic pancreatitis model rats, we identified pancreatic stellate cells as a main source of Fractalkine expression. In vitro study, we confirmed the increased secretion of Fractalkine induced by pathogen-associated molecular patterns, such as LPS, in pancreatic stellate cells. Interestingly, both PMA and ethanol, which were substrates for protein kinase C, could synergistically induce Fractalkine release. Furthermore, we elucidated multiple stress kinase and metalloprotease involving in Fractalkine release by inhibitory assays. In conclusion, it is suggested that Fractalkine plays an important factor in progression of chronic pancreatitis.
|
