Journal
CYTOKINE
Volume 55, Issue 3, Pages 441-445Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2011.03.023
Keywords
Toll-like receptor; Diabetes; Inflammation; Complications; Cytokine
Funding
- Juvenile Diabetes Research Foundation
- American Diabetes Association
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Type 1 diabetes (T1DM) is associated with increased vascular complications and is a pro-inflammatory state. Recent findings have shown increased TLR2 and 4 expression, signaling, ligands, and functional activation in T1DM subjects compared to controls and further accentuated in T1DM with microvascular complications. Thus, the aim of this study was to examine if genetic deficiency of TLR4 attenuates the increased inflammation associated with T1DM using the streptozotocin-induced diabetic mouse model. C57BL/6 and TLR4(-/-) mice were obtained and studied in the native state and following induction of diabetes using streptozotocin. Diabetic (WT + STZ) mice had increased expression of both TLR2 and TLR4, while TLR4(-/-) STZ mice had increased expression only of TLR2, but not TLR4 compared to the non-diabetic mice TLR2 expression was significantly increased with STZ-induced diabetes and was unaffected by knockout of TLR4. Also, levels of MyD88, IRAK-1 protein phosphorylation, Trif, IRF3, and NF-kappa B activity were significantly reduced in TLR4(-/-) +STZ mice compared to the WT + STZ mice. WT + STZ mice exhibited significantly increased levels of serum and macrophage IL-1 beta, IL-6, KC/IL-8, IP-10, MCP-1, IFN beta and TNF-alpha compared to WT mice and this was significantly attenuated in TLR4(-/-) +STZ mice (P < 0.01). Thus, TLR4 contributes to the pro-inflammatory state and TLR4KO attenuates inflammation in diabetes. Published by Elsevier Ltd.
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