Cytokines stimulate dipeptidyl peptidase-IV expression on human luteinizing granulosa cells

We have previously reported that dipeptidyl peptidase-IV (DPPIV) is a differentiation antigen for human granulosa cells that is initially expressed during corpus luteum formation. To investigate the involvement of cytokines in luteal cell differentiation, we examined the expression and activity of DPPIV in human luteinizing granulosa cells cultured in vitro. Human granulosa cells obtained from patients who had undergone in vitro fertilization were cultured for 7 days in the absence (controls) or presence of hCG (1 U/mL), tumor necrosis factor-alpha (TNF alpha; 10 ng/mL), or interleukin 1-alpha (IL-1 alpha; 10 ng/mL). Flow cytometry showed that the percentage of cultured granulosa cells treated with TNF alpha and IL-1 alpha that was positive for DPPIV expression was significantly higher than that in controls (43.7 +/- 5.4% and 43.4 +/- 5.6%, respectively, vs. 21.7 +/- 3.5%; P < 0.01), whereas hCG treatment produced no remarkable difference in DPPIV expression (24.0 +/- 5.2%). The DPPIV activity of cells treated with TNF alpha and IL-1 alpha was also significantly higher than that of controls, whereas hCG treatment produced no significant difference from control values. These findings indicate that TNF alpha and IL-1 alpha stimulate DPPIV expression and activity in human luteinizing granulosa cells in vitro and suggest the involvement of cytokines in the differentiation of granulosa cells during corpus luteum formation.