Next Article in Journal
HPLC-DAD-ESI/MS Identification and Quantification of Phenolic Compounds in Ilex paraguariensis Beverages and On-Line Evaluation of Individual Antioxidant Activity
Previous Article in Journal
Retraction: Sasidharan et al. Evaluation of the Hepatoprotective Effects of Lantadene A, a Pentacyclic Triterpenoid of Lantana Plants against Acetaminophen-induced Liver Damage. Molecules 2012, 17, 13937-13947
Molecules 2013, 18(4), 3841-3858; doi:10.3390/molecules18043841
Article

Phenylmethimazole Suppresses dsRNA-Induced Cytotoxicity and Inflammatory Cytokines in Murine Pancreatic Beta Cells and Blocks Viral Acceleration of Type 1 Diabetes in NOD Mice

1,2,3,4,5,6,* , 7, 3, 2,3,5, 1, 2,5,6, 2,3,5,6 and 1,3,6
Received: 16 February 2013; in revised form: 28 February 2013 / Accepted: 22 March 2013 / Published: 27 March 2013
Download PDF [520 KB, uploaded 18 June 2014]
Abstract: Accumulating evidence supports a role for viruses in the pathogenesis of type 1 diabetes mellitus (T1DM). Activation of dsRNA-sensing pathways by viral dsRNA induces the production of inflammatory cytokines and chemokines that trigger beta cell apoptosis, insulitis, and autoimmune-mediated beta cell destruction. This study was designed to evaluate and describe potential protective effects of phenylmethimazole (C10), a small molecule which blocks dsRNA-mediated signaling, on preventing dsRNA activation of beta cell apoptosis and the inflammatory pathways important in the pathogenesis of T1DM. We first investigated the biological effects of C10, on dsRNA-treated pancreatic beta cells in culture. Cell viability assays, quantitative real-time PCR, and ELISAs were utilized to evaluate the effects of C10 on dsRNA-induced beta cell cytotoxicity and cytokine/chemokine production in murine pancreatic beta cells in culture. We found that C10 significantly impairs dsRNA-induced beta cell cytotoxicity and up-regulation of cytokines and chemokines involved in the pathogenesis of T1DM, which prompted us to evaluate C10 effects on viral acceleration of T1DM in NOD mice. C10 significantly inhibited viral acceleration of T1DM in NOD mice. These findings demonstrate that C10 (1) possesses novel beta cell protective activity which may have potential clinical relevance in T1DM and (2) may be a useful tool in achieving a better understanding of the role that dsRNA-mediated responses play in the pathogenesis of T1DM.
Keywords: type 1diabetes; dsRNA; beta cell death; phenylmethimazole (C10) type 1diabetes; dsRNA; beta cell death; phenylmethimazole (C10)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

McCall, K.D.; Schmerr, M.J.; Thuma, J.R.; James, C.B.L.; Courreges, M.C.; Benencia, F.; Malgor, R.; Schwartz, F.L. Phenylmethimazole Suppresses dsRNA-Induced Cytotoxicity and Inflammatory Cytokines in Murine Pancreatic Beta Cells and Blocks Viral Acceleration of Type 1 Diabetes in NOD Mice. Molecules 2013, 18, 3841-3858.

AMA Style

McCall KD, Schmerr MJ, Thuma JR, James CBL, Courreges MC, Benencia F, Malgor R, Schwartz FL. Phenylmethimazole Suppresses dsRNA-Induced Cytotoxicity and Inflammatory Cytokines in Murine Pancreatic Beta Cells and Blocks Viral Acceleration of Type 1 Diabetes in NOD Mice. Molecules. 2013; 18(4):3841-3858.

Chicago/Turabian Style

McCall, Kelly D.; Schmerr, Martin J.; Thuma, Jean R.; James, Calvin B.L.; Courreges, Maria C.; Benencia, Fabian; Malgor, Ramiro; Schwartz, Frank L. 2013. "Phenylmethimazole Suppresses dsRNA-Induced Cytotoxicity and Inflammatory Cytokines in Murine Pancreatic Beta Cells and Blocks Viral Acceleration of Type 1 Diabetes in NOD Mice." Molecules 18, no. 4: 3841-3858.


Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert