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Though Active on RINm5F Insulinoma Cells and Cultured Pancreatic Islets, Recombinant IL-22 Fails to Modulate Cytotoxicity and Disease in a Protocol of Streptozotocin-Induced Experimental Diabetes

Overview of attention for article published in Frontiers in Pharmacology, January 2016
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Title
Though Active on RINm5F Insulinoma Cells and Cultured Pancreatic Islets, Recombinant IL-22 Fails to Modulate Cytotoxicity and Disease in a Protocol of Streptozotocin-Induced Experimental Diabetes
Published in
Frontiers in Pharmacology, January 2016
DOI 10.3389/fphar.2015.00317
Pubmed ID
Authors

Anika Berner, Malte Bachmann, Christine Bender, Josef Pfeilschifter, Urs Christen, Heiko Mühl

Abstract

Interleukin (IL)-22 is a cytokine displaying tissue protective and pro-regenerative functions in various preclinical disease models. Anti-bacterial, pro-proliferative, and anti-apoptotic properties mediated by activation of the transcription factor signal transducer and activator of transcription (STAT)-3 are key to biological functions of this IL-10 family member. Herein, we introduce RINm5F insulinoma cells as rat β-cell line that, under the influence of IL-22, displays activation of STAT3 with induction of its downstream gene targets Socs3, Bcl3, and Reg3b. In addition, IL-22 also activates STAT1 in this cell type. To refine those observations, IL-22 biological activity was evaluated using ex vivo cultivated murine pancreatic islets. In accord with data on RINm5F cells, islet exposure to IL-22 activated STAT3 and upregulation of STAT3-inducible Socs3, Bcl3, and Steap4 was evident under those conditions. As these observations supported the hypothesis that IL-22 may exert protective functions in toxic β-cell injury, application of IL-22 was investigated in murine multiple-low-dose streptozotocin (STZ)-induced diabetes. For that purpose, recombinant IL-22 was administered thrice either immediately before and at disease onset (at d4, d6, d8) or closely thereafter (at d8, d10, d12). These two IL-22-treatment periods coincide with two early peaks of β-cell injury detectable in this model. Notably, none of the two IL-22-treatment strategies affected diabetes incidence or blood glucose levels in STZ-treated mice. Moreover, pathological changes in islet morphology analyzed 28 days after disease induction were not ameliorated by IL-22 administration. Taken together, despite being active on rat RINm5F insulinoma cells and murine pancreatic islets, recombinant IL-22 fails to protect pancreatic β-cells in the tested protocols from toxic effects of STZ and thus is unable to ameliorate disease in the widely used model of STZ-induced diabetes.

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Mendeley readers

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The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 25%
Student > Ph. D. Student 2 13%
Student > Master 2 13%
Student > Bachelor 1 6%
Other 1 6%
Other 0 0%
Unknown 6 38%
Readers by discipline Count As %
Agricultural and Biological Sciences 4 25%
Biochemistry, Genetics and Molecular Biology 3 19%
Medicine and Dentistry 2 13%
Earth and Planetary Sciences 1 6%
Unknown 6 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 January 2016.
All research outputs
#20,300,248
of 22,837,982 outputs
Outputs from Frontiers in Pharmacology
#10,074
of 16,077 outputs
Outputs of similar age
#331,825
of 395,128 outputs
Outputs of similar age from Frontiers in Pharmacology
#48
of 73 outputs
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