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Cathelicidins posit...
Cathelicidins positively regulate pancreatic beta-cell functions
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- Sun, Jia (author)
- Jiangnan Univ, Ctr Food Safety & Nutr, Sch Food Sci & Technol & Synerget Innovat, State Key Lab Food Sci & Technol, Wuxi 214122, Peoples R China.
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- Xu, Meng (author)
- Uppsala universitet,Institutionen för kemi - BMC
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- Ortsäter, Henrik (author)
- Karolinska Inst, Dept Clin Sci & Educ, Diabet Res Unit, Stockholm, Sweden.
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- Lundeberg, Erik (author)
- Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
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- Juntti-Berggren, Lisa (author)
- Karolinska Institutet
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- Chen, Yong Q. (author)
- Jiangnan Univ, Ctr Food Safety & Nutr, Sch Food Sci & Technol & Synerget Innovat, State Key Lab Food Sci & Technol, Wuxi 214122, Peoples R China.
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- Haeggström, Jesper Z. (author)
- Karolinska Institutet,Uppsala universitet,Institutionen för kemi - BMC
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- Gudmundsson, Gudmundur H. (author)
- Univ Iceland, Biomed Ctr, Reykjavik, Iceland.
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- Diana, Julien (author)
- CNRS, INSERM, Inst Necker Enfants Malades, Paris, France.;Univ Paris 05, Sorbonne Paris Cite, Paris, France.
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- Agerberth, Birgitta (author)
- Karolinska Institutet
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Jiangnan Univ, Ctr Food Safety & Nutr, Sch Food Sci & Technol & Synerget Innovat, State Key Lab Food Sci & Technol, Wuxi 214122, Peoples R China Institutionen för kemi - BMC (creator_code:org_t)
- 2015-11-02
- 2016
- English.
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In: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 30:2, s. 884-894
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Cathelicidins are pleiotropic antimicrobial peptides largely described for innate antimicrobial defenses and, more recently, immunomodulation. They are shown to modulate a variety of immune or nonimmune host cell responses. However, how cathelicidins are expressed by beta cells and modulate beta-cell functions under steady-state or proinflammatory conditions are unknown. We find that cathelicidin-related antimicrobial peptide (CRAMP) is constitutively expressed by rat insulinoma b-cell clone INS-1 832/13. CRAMP expression is inducible by butyrate or phenylbutyric acid and its secretion triggered upon inflammatory challenges by IL-1 beta or LPS. CRAMP promotes b-cell survival in vitro via the epidermal growth factor receptor (EGFR) and by modulating expression of antiapoptotic Bcl-2 family proteins: p-Bad, Bcl-2, and Bcl-xL. Also via EGFR, CRAMP stimulates glucose-stimulated insulin secretion ex vivo by rat islets. A similar effect is observed in diabetes-prone nonobese diabetic (NOD) mice. Additional investigation under inflammatory conditions reveals that CRAMP modulates inflammatory responses and beta-cell apoptosis, asmeasured by prostaglandin E2 production, cyclooxygenases (COXs), and caspase activation. Finally, CRAMP-deficient cnlp(-/-) mice exhibit defective insulin secretion, and administration of CRAMP to prediabetic NOD mice improves blood glucose clearance upon glucose challenge. Our finding suggests that cathelicidins positively regulate beta-cell functions and may be potentially used for intervening b-cell dysfunction-associated diseases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- antimicrobial peptide
- CRAMP
- immunomodulation
- endocrine cells
- type 1 diabetes
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Sun, Jia
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Xu, Meng
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Ortsäter, Henrik
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Lundeberg, Erik
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Juntti-Berggren, ...
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Chen, Yong Q.
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Haeggström, Jesp ...
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Gudmundsson, Gud ...
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Diana, Julien
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Agerberth, Birgi ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
- Articles in the publication
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The FASEB Journa ...
- By the university
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Uppsala University
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Karolinska Institutet