CCL28 Has a Dual Role in Mucosal Immunity as Chemokine with a Broad-Spectrum Antimicrobial Activity
| Project/Area Number |
14570289
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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 |
Immunology
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| Research Institution | Kinki University |
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Principal Investigator |
HIESHIMA Kunio Kinki University, Dept of Microbiol., Assistant Professor, 医学部, 講師 (10322570)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIE Osamu Kinki University, Dept of Microbiol., Professor, 医学部, 教授 (10166910)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | chemokine / exocrine gland / salivary gland / antimicrobial activity / plasma cells / mucosal immunity |
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| Research Abstract |
CCL28 is a CC chemokine selectively expressed in the salivary glands, mammary glands and colon. We found that CCL28 is constitutively expressed and secreted by the salivary glands and has a dual role as a chemoattractant for B220^<low>CD3^-IgA^+ plasma cells expressing OCR10, receptor for CCL28, and as a potent antimicrobial protein. Serous acinar epithelial cells of human and mouse salivary glands were strongly positive for CCL28 and human whole and parotid saliva contained CCL28 at high concentrations. We also noticed a sequence similarity between the C-terminal region of human CCL28 and human histatin-5, a histidine-rich cationic peptide in human saliva with a potent candidacidal activity. We demonstrated that human and mouse CCL28 had a broad spectrum of antimicrobial activity against Candida albicans, Gram-negative bacteria and Gram-positive bacteria We also demonstrated that the C-terminal 28-amino acid domain of human CCL28 has a selective candklacidal activity as histatin-5. On the other hand, we found no such potent antimicrobial activity with CCL27, which is most closely related to CCL28 and shares CCR10 with CCL28. Finally, we demonstrated that the antimicrobial activity of CCL28 is sensitive to high salt concentrations, as with most other antimicrobial peptides, and displays a rapid induction of membrane permeability in target microbes under scanning electron microscopy In conclusion, CCL28 has a dual role in mucosal immunity as a chemoattractant and as a secreted molecule with a potent antimicrobial activity
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Report
(3 results)
Research Products
(10 results)
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[Publications] Hieshima K, Ohtani H, Shibano M, Izawa D, Nakayama T, Kawasaki Y, Shiba F, Shiota M, Katou F, Saito T, Yoshie O: "CCL28 has dual roles in mucosal immunity as a chemokine with broad-spectrum antimicrobial activity"Journal of Immunology. 170(3). 1452-1461 (2003)
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