Abstract
Background:
Autoimmune diseases are characterized by a breakdown of immunologic tolerance, and this breakdown can lead to life-threatening or lifelong disorders. Moreover; drugs that are used to treat these diseases are few in number and are associated with many serious adverse effects.
Methods:
We used the rat insulin promoter-glycoprotein mouse model to analyze the role of tunicamycin in the process of autoimmune diabetes; the P14 mouse model to analyze the effect of tunicamycin on CD8(+) T cells; chop knockout mice to analyze the role of tunicamycin on an endoplasmic reticulum stress model; and fluorescence-activated cell sorting, quantitative real-time polymerase chain reaction, and histologic methods.
Results:
We found that a single dose of tunicamycin reduced the activation and pancreatic infiltration of CD8(+) T cells. This activity delayed the incidence of virus-induced diabetes and improved survival rates.
Conclusion:
Tunicamycin may offer therapeutic opportunities for T cell-mediated autoimmune diseases such as diabetes.
Copyright © 2012 S. Karger AG, Basel.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Apoptosis
-
Autoimmune Diseases / drug therapy
-
Autoimmune Diseases / immunology
-
Autoimmune Diseases / pathology
-
Autoimmune Diseases / virology
-
Blood Glucose / drug effects
-
Blood Glucose / metabolism
-
CD8-Positive T-Lymphocytes / drug effects*
-
Cell Proliferation / drug effects
-
Cytokines / drug effects
-
Cytokines / metabolism
-
Diabetes Mellitus, Experimental / drug therapy*
-
Diabetes Mellitus, Experimental / immunology
-
Diabetes Mellitus, Experimental / pathology
-
Diabetes Mellitus, Experimental / virology
-
Endoplasmic Reticulum Stress
-
Flow Cytometry
-
Glycoproteins / genetics
-
Glycoproteins / immunology
-
Glycoproteins / metabolism
-
Hypoglycemic Agents / administration & dosage
-
Hypoglycemic Agents / therapeutic use*
-
Immunosuppressive Agents / immunology
-
Immunosuppressive Agents / therapeutic use
-
Lymphocyte Activation / drug effects
-
Lymphocytic choriomeningitis virus / chemistry
-
Lymphocytic choriomeningitis virus / immunology
-
Lymphocytic choriomeningitis virus / pathogenicity
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Pancreas / metabolism
-
Pancreas / pathology
-
Promoter Regions, Genetic
-
Rats
-
Reverse Transcriptase Polymerase Chain Reaction
-
Transcription Factor CHOP / genetics
-
Transcription Factor CHOP / metabolism
-
Tunicamycin / therapeutic use*
Substances
-
Blood Glucose
-
Cytokines
-
Ddit3 protein, mouse
-
Glycoproteins
-
Hypoglycemic Agents
-
Immunosuppressive Agents
-
Tunicamycin
-
Transcription Factor CHOP