In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 112, No. 15 ( 2005-10-11), p. 2276-2285
Abstract:
Background— Myeloid differentiation factor (MyD)-88 is a key adaptor protein that plays a major role in the innate immune pathway. How MyD88 may regulate host response in inflammatory heart disease is unknown. Methods and Results— We found that the cardiac protein level of MyD88 was significantly increased in the hearts of wild-type mice after exposure to Coxsackievirus B3 (CVB3). MyD88 −/− mice showed a dramatic higher survival rate (86%) in contrast to the low survival (35%) in the MyD88 +/+ mice after CVB3 infection ( P 〈 0.0001). Pathological examination showed a significant decrease of cardiac and pancreatic inflammation in the MyD88 −/− mice. Viral concentrations in the hearts were significantly decreased in the MyD88 −/− mice. Cardiac mRNA levels for interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-18 were significantly decreased in the MyD88 −/− mice. Similarly, serum levels of T-helper 1 cytokines were significantly decreased in the MyD88 −/− mice. In contrast, cardiac protein levels of the activated interferon regulatory factor (IRF)-3 and IFN-β were significantly increased in the MyD88 −/− mice but not other usual upstream signals to IRF-3. The cardiac expression of coxsackie-adenoviral receptor and p56 lck were also significantly decreased. Conclusions— MyD88 appears to be a key contributor to cardiac inflammation, mediating cytokine production and T-helper-1/2 cytokine balance, increasing coxsackie-adenoviral receptor and p56 lck expression and viral titers after CVB3 exposure. Absence of MyD88 confers host protection possibly through novel direct activation of IRF-3 and IFN-β.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/CIRCULATIONAHA.105.536433
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2005
detail.hit.zdb_id:
1466401-X
