| First Author | Mirza RE | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 7 | Pages | 2579-87 |
| PubMed ID | 23493576 | Mgi Jnum | J:208666 |
| Mgi Id | MGI:5563893 | Doi | 10.2337/db12-1450 |
| Citation | Mirza RE, et al. (2013) Blocking interleukin-1beta induces a healing-associated wound macrophage phenotype and improves healing in type 2 diabetes. Diabetes 62(7):2579-87 |
| abstractText | Diabetes is associated with persistent inflammation and defective tissue repair responses. The hypothesis of this study was that interleukin (IL)-1beta is part of a proinflammatory positive feedback loop that sustains a persistent proinflammatory wound macrophage phenotype that contributes to impaired healing in diabetes. Macrophages isolated from wounds in diabetic humans and mice exhibited a proinflammatory phenotype, including expression and secretion of IL-1beta. The diabetic wound environment appears to be sufficient to induce these inflammatory phenomena because in vitro studies demonstrated that conditioned medium of both mouse and human wounds upregulates expression of proinflammatory genes and downregulates expression of prohealing factors in cultured macrophages. Furthermore, inhibiting the IL-1beta pathway using a neutralizing antibody and macrophages from IL-1 receptor knockout mice blocked the conditioned medium-induced upregulation of proinflammatory genes and downregulation of prohealing factors. Importantly, inhibiting the IL-1beta pathway in wounds of diabetic mice using a neutralizing antibody induced a switch from proinflammatory to healing-associated macrophage phenotypes, increased levels of wound growth factors, and improved healing of these wounds. Our findings indicate that targeting the IL-1beta pathway represents a new therapeutic approach for improving the healing of diabetic wounds. |
