To elucidate the expression and effect of TLR4 on pancreatic β-cells, we studied mouse islets and the murine β-cell line MIN6 in the presence of macrophages (MΦ). Diabetic islets had 40% less TLR4+ β-cells, while twice as many TLR4+ MΦ compared to healthy islets. TLR4 activation with LPS induced a 5-10 fold induction of cytokines in healthy and diabetic islets. MIN6 cells were only weakly TLR4+ and did not produce cytokines in response to LPS. LPS stimulated diabetic systemic MΦ released 3-10 fold more cytokines per cell compared to healthy MΦ. Interestingly, diabetic MΦ co-cultured with MIN6 cells secreted higher levels of cytokines compared to MΦ alone. We also measured apoptosis in healthy and diabetic islets treated with LPS and found no effect. However, a 3-fold induction of MIN6 apoptosis was obtained when co-cultured with diabetic MΦ and 2-fold when cultured with media from LPS activated MΦ. Taken together, our data suggest that the majority of the TLR4 response in the islet appears to be mediated through MΦ. Moreover a cell-dependent MΦ- β-cell interaction appears to contribute to the enhanced local immunity in the islet. Thus targeting either TLR4 or macrophages may provide a novel treatment regime for type 2 diabetes.
- Copyright © 2013 by The American Association of Immunologists, Inc.