effect of AT[1] receptor blockade on BAX and BCL-2 expression in bleomycin-induced pulmonary fibrosis

Recent studies have indicated the role of apoptosis and angiotensin in the pathogenesis of bleomycin induced-pulmonary fibrosis. Losartan, an angiotensin type 1 receptor [AT1R] antagonist, has ameliorated apoptosis and fibrosis from bleomycin. In this study, alterations in the expression of apoptosis-regulatory genes [bcl-2 and bax] were investigated in different cells of lung tissue of mice treated with bleomycin in the presence of losartan. Losartan [10 mg/kg, i.p.] was given to mice two days before administration of bleomycin [3 U/kg] and throughout the test period. After two weeks, lung tissues of mice were evaluated for fibrosis by biochemical measurement of collagen deposition and semiquantitative analysis of pathological changes of the lung. The expression of bcl-2 and bax was assessed by immunohistochemical assay using biotin-streptavidin staining method on paraffin-embedded lung tissues. Pre-treatment with losartan significantly [P < 0.05] reduced the increase in lung collagen content and also inhibited the histological changes induced by bleomycin. Immunohistochemical studies showed that losartan significantly [P < 0.05] reduced the bax/bcl-2 expression ratio in the alveolar epithelial cells, lymphocytes, macrophages and interstitial myofibroblasts. Losartan also inhibited the bcl-2 upregulation which was educed by bleomycin in neutrophils. By reduction of bax/bcl-2 ratio as a determinant of susceptibility of a cell to apoptosis, losartan exerted protective effects on the alveolar epithelial cells that may be important in the amelioration of pulmonary fibrosis. These results may help to better understanding of the role of angiotensin II and apoptosis in pulmonary fibrosis

Study of myoepithelial cell markers in pleomorphic adenoma and mucoepidermoid carcinoma of salivary glands

The application of immunohistochemical method has resulted in marked improvement of the microscopic diagnosis of neoplasms combined with H and E staining. Although unique cellular antigens have not been found in salivary gland neoplasms, multiple less specific immunomarkers have been used and may be helpful in elucidating the role of myoepithelial differentiation in those neoplasms. The aim of this study was to evaluate immunohistochemical myoepithelial markers [GFAP, actin, vimentin, and S100] in mucoepidermoid carcinoma and pleomorphic adenoma of salivary glands for differential diagnosis of these tumors and specification of their histogenesis. Formalin-fixed and parafin embedded tissue sections of 25 pleomorphic adenoma and 25 mucoepidermoid carcinoma were immunohistochemically analyzed for the presence of actin, vimentin, GFAP, and S100 protein. A standard biotin-streptavidin procedure was used after antigen retrieval. Immunoreactivity of myoepithlial cells and chondromyxoid areas in pleomorphic adenoma and mucus cell, epidermoid cells, and intermediate cells in mucoepidermoid carcinoma were evaluated and immunoreactivity was scored on a scale of 0 to +4 [Regezi method] with o as negative, 1+ as scattered staining, 2+ as 25% to 50% of positive tumoral cells, and 4+ as more than 50% positive cells. The data were analyzed with chi-square test, and significance level was considered as 0.05 [P<0.05]. In 25 pleomorphic adenomas, all nonluminal cells and chondromyxoid areas were positive [+4] for GFAP and vimentin and [03+3] for muscle-specific actin [12:0, 12:+1, 1:+3] and [+13+4] for S100 protein [3:+1, 3:+2, 18:+3, 1:+4]. But all mentioned markers were negative for all mucoepidermoid carcinomas, regardless of their grades [P<0.001] and there were no immunohistochemical difference in major and minor salivary glands neoplasms. Expression of myoepithelial cell-associated markers in pleomorphic adenoma have confirmed role of myoepithelial the cells in histogenesis of this tumor and lack or limited expression of these antigens in mucoepidermoid carcinoma, indicate the minimal myoepithelial differentiation in this tumor. Therefore, evaluation of myoepithelial cell markers can be helpful in differential diagnosis of salivary gland neoplasms with myoepithelial cell differentiation, and also specification of histogenesis of these tumors