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Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes

Hodik, M ; Anagandula, M ; Fuxe, J ; Krogvold, L ; Dahl-Jørgensen, K ; Hyöty, H ; Sarmiento, L and Frisk, G (2016) In BMJ open diabetes research & care 4(1). p.000219-000219
Abstract

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... (More)

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.

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author collaboration
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Contribution to journal
publication status
published
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in
BMJ open diabetes research & care
volume
4
issue
1
pages
000219 - 000219
publisher
BMJ Publishing Group
external identifiers
  • scopus:84998774606
  • pmid:27933184
ISSN
2052-4897
DOI
10.1136/bmjdrc-2016-000219
language
English
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no
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71e060db-debc-41e4-9b84-8e5839a57ca5
date added to LUP
2019-07-08 14:15:52
date last changed
2020-02-26 07:32:19
@article{71e060db-debc-41e4-9b84-8e5839a57ca5,
  abstract     = {<p>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.</p><p>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.</p><p>RESULTS: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p&lt;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&lt;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&lt;0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR.</p><p>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.</p>},
  author       = {Hodik, M and Anagandula, M and Fuxe, J and Krogvold, L and Dahl-Jørgensen, K and Hyöty, H and Sarmiento, L and Frisk, G},
  issn         = {2052-4897},
  language     = {eng},
  number       = {1},
  pages        = {000219--000219},
  publisher    = {BMJ Publishing Group},
  series       = {BMJ open diabetes research & care},
  title        = {Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes},
  url          = {http://dx.doi.org/10.1136/bmjdrc-2016-000219},
  doi          = {10.1136/bmjdrc-2016-000219},
  volume       = {4},
  year         = {2016},
}