HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: db06-0495v1 56/5/1240    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hu, C.-M. Articles by Chau, L.-Y. Search for Related Content PubMed PubMed Citation Articles by Hu, C.-M. Articles by Chau, L.-Y. Social Bookmarking                What's this?

Systemic Expression of Heme Oxygenase-1 Ameliorates Type 1 Diabetes in NOD Mice

From the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China

Address correspondence and reprint requests to Lee-Young Chau, PhD, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China. E-mail: lyc{at}ibms.sinica.edu.tw

Abbreviations: AAV, adeno-associated virus; APC, antigen-presenting cell; ConA, concanavalin A; FITC, fluorescein isothiocyanate; HO-1, heme oxygenase-1; IFN-, -interferon; IL, interleukin; MHC, major histocompatibility complex; PBST, PBS containing 0.1% Tween-20; PMSF, phenylmethylsulfonyl fluoride; Th1, type 1 T-helper cell; Treg cells, regulatory T cells

Heme oxygenase-1 (HO-1) is an enzyme with potent immunoregulatory capacity. To evaluate the effect of HO-1 on autoimmune diabetes, female NOD mice at 9 weeks of age received a single intravenous injection of a recombinant adeno-associated virus bearing HO-1 gene (AAV-HO-1; 0.5 x 10¹⁰-2.5 x 10¹⁰ viruses/mouse). In a dose-dependent manner, HO-1 transduction reduced destructive insulitis and the incidence of overt diabetes examined over a 15-week period. HO-1–mediated protection was associated with a lower type 1 T-helper cell (Th1)–mediated response. Adaptive transfer experiments in NOD.scid mice demonstrated that splenocytes isolated from AAV-HO-1–treated mice were less diabetogenic. Flow cytometry analysis revealed no significant difference in the percentages of CD4⁺CD25⁺ regulatory T-cells between saline-treated and AAV-HO-1–treated groups. However, the CD11c⁺ major histocompatibility complex II⁺ dendritic cell population was much lower in the AAV-HO-1–treated group. A similar protective effect against diabetes was observed in NOD mice subjected to carbon monoxide (CO) gas (250 ppm CO for 2 h, twice per week). These data suggest that HO-1 slows the progression to overt diabetes in pre-diabetic NOD mice by downregulating the phenotypic maturity of dendritic cells and Th1 effector function. CO appears to mediate at least partly the beneficial effect of HO-1 in this disease setting.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?