alexa Interferon-gamma increases the sensitivity of islets of Langerhans for inducible nitric-oxide synthase expression induced by interleukin 1.


Immunome Research

Author(s): Heitmeier MR, Scarim AL, Corbett JA, Heitmeier MR, Scarim AL, Corbett JA

Abstract Share this page

Abstract The purpose of this study was to evaluate the effects of interferon-gamma (IFN-gamma) alone and in combination with interleukin 1beta (IL-1beta) on inducible nitric-oxide synthase (iNOS) mRNA and protein expression, nitrite production, and insulin secretion by islets of Langerhans. Treatment of rat islets with IL-1beta results in a concentration-dependent increase in the production of nitrite that is maximal at 5 units/ml. Individually, 0. 1 unit/ml IL-1beta or 150 units/ml rat IFN-gamma do not stimulate iNOS expression or nitrite production by rat islets; however, in combination, these cytokines induce the expression of iNOS and the production of nitrite to levels similar in magnitude to the individual effects of 5 units/ml IL-1beta. The islet beta-cell, selectively destroyed during insulin-dependent diabetes mellitus, appears to be one islet cellular source of iNOS as 150 units/ml rat IFN-gamma and 0.1 unit/ml IL-1beta induced similar effects in primary beta-cells purified by fluorescence-activated cell sorting and in the rat insulinoma cell line, RINm5F. iNOS expression and nitrite production by rat islets in response to 150 units/ml rat IFN-gamma and 0.1 unit/ml IL-1beta are correlated with an inhibition of insulin secretion and islet degeneration that are prevented by the iNOS inhibitor aminoguanidine. The mechanism by which IFN-gamma increases the sensitivity of beta-cells for IL-1-induced iNOS expression appears to be associated with an increase in the stability of iNOS mRNA. Last, cellular damage during physical dispersion of islets results in the release of sufficient amounts of IL-1beta to induce iNOS expression and nitrite production in the presence of exogenously added rat IFN-gamma. The cellular source of IL-1beta under these conditions is believed to be resident islet macrophages as depletion of macrophages prior to dispersion prevents IFN-gamma-induced iNOS expression and nitrite formation by dispersed islet cells. These studies show that the T-lymphocyte cytokine, IFN-gamma, increases the sensitivity of rat islets to the effects of IL-1beta on iNOS expression and nitrite production by 10-fold, in part, through the stabilization of iNOS mRNA. Our studies also support an effector role for IFN-gamma, in concert with resident islet macrophage release of IL-1beta, in mediating beta-cell destruction during the development of autoimmune diabetes.
This article was published in J Biol Chem and referenced in Immunome Research

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

1-702-714-7001Extn: 9037

Business & Management Journals


1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

1-702-714-7001Extn: 9042

General Science

Andrea Jason

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

1-702-714-7001Extn: 9042

© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version