Objective: To study the effect of pentoxifylline (PTX) on promoter activity of human alpha 1(I) procollagen (COL1A1) gene and the influence of PTX on the promoter activity induced by insulin-like growth factor 1 and insulin.
Methods: The constructs of pCOLH2.5 containing -2483 approximately +42bp of the procollagen gene and chloramphenicol acetyltransferase (CAT) as reporter gene were transiently transfected into human skin fibroblasts. The cells were subsequently treated with PTX or IGF-1 or insulin, or PTX plus IGF-1 or insulin. The CAT activity was assessed 24h after PTX and the cytokines added.
Results: PTX of 0.4 mmol/L, 2 mmol/L, and 10 mmol/L decreased the CAT activity of pCOLH 2.5 to 82%+/-9%, 58%+/-8%, and 32%+/-13% of the control level, respectively. IGF-1 and insulin increased the activity of the construct. PTX could inhibit the CAT activity of pCOLH2.5 induced by IGF-1 and insulin.
Conclusions: These studies indicate that PTX downregulates the promoter activity of the human COL1A1 gene, while IGF-1 and insulin upregulates it. PTX can inhibit the promoter activity induced by IGF-1 and insulin.