BackgroundIt is now well established that IL-4 has a central role in the development of monocytes to multinucleated giant cells (MGCs) by inducing the expression of integrins on the surface of monocytes. The aim of this study was to investigate the potential role of IL-4 in induction of β5 integrin expression in the peripheral blood samples of patients with giant cell granuloma.Material and MethodsMonocytes were isolated from peripheral blood samples of patients with central giant cell granuloma (CGCG) and healthy controls using human Monocyte Isolation Kit II. Isolated monocytes were then cultured in the absence or presence of IL-4 (10 and 20 ng/mL), and following RNA extraction and cDNA synthesis, Real-time PCR was performed to determine the level of β5 integrin expression. The formation of CGCGs and morphological analyses were done under light microscopy. For confirmation of CGCGs, immunocytochemistry technique was also carried out by anti-RANK (receptor-activator of NF-κB ligand) antibody.ResultsIn both patient and control groups, β5 levels were significantly enhanced by increasing the IL-4 dose from 10 to 20 ng/mL. In addition, these differences were significant between patient and control groups without IL-4 treatment. On the other hand, the number of cells which expressed RANK and therefore the number of giant cells were significantly higher in the patient group in comparison to controls, as assessed by immunohistochemistry evaluations.ConclusionsIn this study, we showed an elevation in the expression levels of β5 integrin when stimulated by IL-4. It is strongly indicated that this integrin acts as an important mediator during macrophage to macrophage fusion and development of giant cells.
Key words:β5 integrin, giant cell, Il-4, monocyte, rank.
Introduction: Breast cancer is one of the common cancers especially among women that occurs all over the world. In spite of clinical and therapeutic progressions in recent years, many of patients also lose their lives after operation and metastasis. Bach1 gene plays a major role in growth of cancer, invasion, metastasis and inhibition of apoptosis in tumor cells. The purpose of this study is to knockdown bach1 gene and survey its effect on expression level of miR-21 and MMP-3. Materials and Methods: In this study which is an experimental study, after designing and making of specific siRNA of the bach1 gene, its transfect on MDA-MB-468 cell lines was applied. Expression level of the gene analyzed by qRT-PCR. Proliferation of the cells examined by means of trypan blue experiment. Metastasis and cell invasion applied by examining of MMP-3 expression. At the end, expression level of miR-21 examined too. Results: A significant decrease in gene expression of bach1 in effective dosage (p=0.001), metastasis and cell invasion was observed and also resulted of bach1 knockdown in a significant decrease in expression of mir-21 (P=0.0014) and MMP-3 (P<0.0001). Conclusions: Bach1 knockdown can play a role in decreasing of breast cancer's impacts particularly in metastasis and its invasion besides, it makes decrease in the expression of metastatic microRNA such as miR-21. Therefore, knockdown of bach1 gene can have an effective therapeutic impact on breast cancer. Bach1 and miR-21 are considered as a diagnostic marker in breast cancer.
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