Epidermal growth factor receptor inhibition by erlotinib prevents vascular smooth muscle cell and monocyte-macrophage function in vitro
| Autor: | Jukka Rintala, Sini E. Rintala, Johanna Savikko, Petri Koskinen |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Graft Rejection
medicine.medical_specialty Vascular smooth muscle medicine.drug_class medicine.medical_treatment Immunology Myocytes Smooth Muscle Tyrosine-kinase inhibitor Monocytes Cell Line Erlotinib Hydrochloride Cell Movement Internal medicine medicine Immunology and Allergy Animals Humans Epidermal growth factor receptor Protein Kinase Inhibitors Cell Proliferation Transplantation biology Monocyte Growth factor Macrophages Cell Differentiation Monocyte proliferation Proto-Oncogene Proteins c-sis musculoskeletal system Coronary Vessels Rats ErbB Receptors medicine.anatomical_structure Endocrinology Chronic Disease cardiovascular system Cancer research biology.protein Erlotinib Endothelium Vascular tissues Platelet-derived growth factor receptor medicine.drug |
| Zdroj: | Transplant immunology. 32(3) |
| ISSN: | 1878-5492 |
| Popis: | Vascular smooth muscle cells (VSMCs) and monocyte-macrophages play a central role during the development of chronic allograft injury, which still remains an important challenge in organ transplantation. Inflammation, fibrosis and accelerated arteriosclerosis are typical features for chronic allograft injury. Growth factors participate in cell proliferation, differentiation and migration in this pathological process.Here we studied the role of epidermal growth factor receptor (EGFR) in VSMC and monocyte-macrophage function in vitro. EGFR inhibition by erlotinib, a selective EGF tyrosine kinase inhibitor, was studied in VSMC proliferation and migration as well as monocyte-macrophage proliferation and differentiation.Rat coronary artery SMCs were used for VSMC studies. As a model for monocyte-macrophage proliferation and differentiation human monocytic cell line U937 was used. Phorbol ester TPA was used to induce these cells to differentiate into macrophages.Platelet-derived growth factor (PDGF)-B, a known VSMC inducer, caused 2.1-fold stimulation in VSMC proliferation compared to non-stimulated VSMC. Erlotinib prevented this VSMC proliferation in a dose-dependent manner, p0.001 in all groups compared to controls. PDGF-B stimulation increased VSMC migration to 2.5-fold when compared with non-stimulated cells. Erlotinib decreased VSMC migration dose-dependently and this effect was significant with all doses, p0.05. Erlotinib inhibited dose-dependently the proliferation of U937 monocytic cells, p0.001. Erlotinib prevented also TPA-induced macrophage differentiation in a dose-dependent way, p0.05.Erlotinib significantly prevents VSMC proliferation and migration in vitro. Erlotinib inhibited also significantly both monocyte proliferation and differentiation. Our data suggest that EGFR inhibition in VSMC and monocyte function has beneficial effects on chronic allograft injury. |
| Databáze: | OpenAIRE |
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