Effects of everolimus and HLA-G on cellular proliferation and neutrophil adhesion in an in vitro model of cardiac allograft vasculopathy
| Autor: | Laura C. Tumiati, Heather J. Ross, Mitchell B. Adamson, A.G. Mociornita, Vivek Rao, Diego H. Delgado |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Neutrophils medicine.medical_treatment Cell Myocytes Smooth Muscle Models Biological 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation HLA-G Cell Adhesion Immunology and Allergy Medicine Humans Pharmacology (medical) Everolimus Vascular Diseases Cells Cultured Cell Proliferation Heart transplantation HLA-G Antigens Transplantation business.industry Adhesion Allografts Coronary Vessels Histocompatibility 030104 developmental biology medicine.anatomical_structure Cancer research Tumor necrosis factor alpha business Immunosuppressive Agents 030215 immunology medicine.drug |
| Zdroj: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 18(12) |
| ISSN: | 1600-6143 |
| Popis: | Human leukocyte antigen-G (HLA-G) expression is modulated by immunosuppressant use and is associated with lower incidence of graft rejection and cardiac allograft vasculopathy (CAV). We examined whether everolimus induces HLA-G expression and inhibits human coronary artery smooth muscle cell (HCASMC) proliferation, a critical event in CAV. Also, we examined whether TNFα-stimulated neutrophil adhesion is inhibited by HLA-G on human coronary artery endothelial cells (HCAECs). HLA-G expression in HCASMCs following everolimus treatment was determined by western-blot densitometric analysis. HCASMCs proliferation following incubation with recombinant HLA-G was determined by automated cell counter detecting 2-10 µm particles. Assessment of recombinant HLA-G on neutrophil adhesion to HCAECs in response to TNF-α induced-injury was determined by nonstatic adhesion assays. HLA-G expression was upregulated in HCASMCs following everolimus exposure (1000 ng/ml; P < .05). HLA-G (500, 1000 ng/ml; both P < .05) reduced HCASMC proliferation and inhibited TNFα-stimulated neutrophil adhesion to endothelial cells at all concentrations (0.1-1 ng/ml; all P < .001). Our study reveals novel regulation of HLA-G by everolimus, by demonstrating HLA-G upregulation and subsequent inhibition of HCASMC proliferation. HLA-G is a potent inhibitor of neutrophil adhesion to HCAECs. Findings support HLA-G's importance and potential use in heart transplantation for preventative therapy or as a marker to identify patients at high risk for developing CAV. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text