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inflammatory cell infiltration as well as less prominent epithelial atrophy and crypt remodeling. In accord, MTX- TGF-b rats manifested a significant decrease in the intestinal injury score in jejunum and ileum compared to MTX animals. MTX-treated rats demonstrated significantly shorter villus heights in jejunum and ileum as well as crypt depth in jejunum compared to control rats . Treatment with TGF-b2 of MTX rats was manifested by a significant increase in villus height in ileum and crypt depth in jejunum compared to MTX animals. Results Cell apoptosis Caco-2 cells were evaluated for apoptosis induction by PI staining. Incubation with TGF-b2 at concentration of 0.5 ng/ml resulted in a significant increase in apoptosis of CaCo-2 cells compared with medium only . Treatment with MTX resulted in a marked increase in cell apoptosis rates over corresponding control cells with vehicle alone. Treatment of MTX-pretreated cells with TGF-b2 at concentrations of 0.1 ng/ ml or 0.5 ng/ml resulted in a significant decrease in the apoptotic rate compared with MTX-treated cells. Cell viability PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/22212322 The LY2109761 changes in cell viability following exposure to MTX and TGF-b are shown in Cell proliferation TGF-b2 Reduces MTX Induced Intestinal Injury cells/10crypts, P,0.05) compared to control rats . Treatment with MTX resulted in a significant decrease in cell proliferation in both the jejunum and ileum compared to control animals. Following TGF-b2 administration, MTX animals demonstrated a significant increase in proliferation rate in the jejunum and ileum compared to the MTX group. Enterocytes apoptosis Administration of TGF-b2 in control rats resulted in a significant increase in cell apoptosis in jejunum and ileum compared to control animals. MTX-induced mucositis was accompanied by a significantly increased cell apoptosis in jejunum and ileum compared to control animals. Treatment of MTX rats with TGF-b resulted in decreased cell apoptosis in ileum compared to MTX animals as well as in a 5 TGF-b2 Reduces MTX Induced Intestinal Injury Expression of Bcl-2 and Bax genes Control-TGF-b animals demonstrated a significant decrease in bax mRNA expression in jejunum and ileum as compared to control rats. Following MTX administration, bax mRNA expression was up-regulated in jejunum and ileum compared to control animals. Treatment of MTX-rats with TGF-b2 attenuated the proapoptotic effects of MTX. MTX-TGF-b rats showed a significant decrease in bax mRNA expression in the jejunum and ileum compared to MTX-animals. Treatment with MTX resulted in a significant down-regulation of bcl-2 mRNA levels in jejunum compared to control rats. MTX-TGF-b rats showed a significant increase in a bcl-2 mRNA expression in jejunum compared to MTX-animals as well as a trend tonward a increase in the bcl-2 mRNA expression in ileum; however this trend was not statistically significant. trend toward a decrease in cell apoptosis in jejunum; however, this decrease was not statistically significant. Western blot for TGF- b receptor CONTR-TGF-b rats demonstrated a significant increase in Type II TGF-b receptor protein as compared to control animals . Treatment with MTX resulted in a trend toward a decrease in Type II TGF-b receptor protein as compared to control rats. Following TGF-b administration, MTX-TGF-b animals demonstrated a significant increase in Type II TGF-b receptor protein as compared to MTX and control rats. TGF-b receptor type II expression along the villus-crypt axis Type II TGF
