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Coxsackie-adenoviru...
Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes
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- Hodik, Monika (författare)
- Uppsala universitet,Klinisk immunologi
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- Anagandula, Mahesh, 1982- (författare)
- Uppsala universitet,Klinisk immunologi
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- Fuxe, J. (författare)
- Karolinska Institutet
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- Krogvold, L. (författare)
- Oslo Univ Hosp, Div Paediat & Adolescent Med, Oslo, Norway.;Univ Oslo, Fac Med, Oslo, Norway.
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- Dahl-Jorgensen, K. (författare)
- Oslo Univ Hosp, Div Paediat & Adolescent Med, Oslo, Norway.;Univ Oslo, Fac Med, Oslo, Norway.
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- Hyoty, H. (författare)
- Univ Tampere, Dept Virol, Tampere, Finland.;Pirkanmaa Hosp Dist, FimlabLabs, Tampere, Finland.
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- Sarmiento, L. (författare)
- Lund Univ, Skane Univ Hosp, Dept Clin Sci, Autoimmun Unit, Malmö, Sweden.
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- Frisk, Gun (författare)
- Uppsala universitet,Klinisk immunologi
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(creator_code:org_t)
- 2016-11-25
- 2016
- Engelska.
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Ingår i: BMJ Open Diabetes Research & Care. - : BMJ. - 2052-4897. ; 4:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://drc.bmj.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Objectives: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie-adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression.Design: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells.Results: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR.Conclusions: CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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