Inactivation of p27kip1 Promoted Nonspecific Inflammation by Enhancing Macrophage Proliferation in Islet Transplantation
| Autor: | Wujun Xue, Yang Li, Xiaohui Tian, Ping Fan, Puxun Tian, Jin Zheng, Jian Guo, Chenguang Ding, Xinshun Feng, Xiaoming Ding |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty geography geography.geographical_feature_category endocrine system diseases Inflammation Biology Islet Proinflammatory cytokine Transplantation 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology 030220 oncology & carcinogenesis Internal medicine medicine Tumor necrosis factor alpha Secretion medicine.symptom Receptor Macrophage proliferation |
| Zdroj: | Endocrinology. 157:4121-4132 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | Islet transplantation suffers from low efficiency caused by nonspecific inflammation-induced graft loss after transplantation. This study reports increased islet loss and enhanced inflammatory response in p27-deficient mice (p27-/-) and proposes a possible mechanism. Compared with wild type, p27-/- mice showed more severe functional injury of islet, with increased serum levels of inflammatory cytokines IL-1 and TNF-α, inducing macrophage proliferation. Furthermore, the increased number, proapoptotic proteins, and nuclear factor-kappa b (NF-κB) phosphorylation status of the infiltrating macrophages were accompanied by increased TNF-α mRNA level of islet graft site in p27-/- mice. Moreover, in vitro, we found that macrophages were still activated and cocultured with islet and promoted islet loss even blocking the direct effect of TNF-α on islets. Malondialdehyde (MDA, an end product of lipid peroxidation) in islet and media were increased after cocultured with macrophages. p27 deficiency also increased macrophage proliferation and islet injury. Therefore, p27 inactivation promotes injury islet graft loss via the elevation of proliferation and inflammatory cytokines secretion in infiltrating macrophages which induced nonspecific inflammation independent of TNF-α/nuclear factor-kappa b pathway. This potentially represents a promising therapeutic target in improving islet graft survival. |
| Databáze: | OpenAIRE |
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