Gene expression profiling of human vaginal cells in vitro discriminates compounds with pro-inflammatory and mucosa-altering properties

Inflammation and immune activation of the cervicovaginal mucosa are considered factors that increase susceptibility to HIV infection. It is essential to screen candidate anti-HIV microbicides for potential mucosal immunomodulatory/inflammatory effects prior to further clinical development. The goal of this study was to develop an in vitro method for preclinical evaluation of the inflammatory potential of new candidate microbicides. We compared transcriptomes of human vaginal cells (Vk2/E6E7) treated with well-characterized pro-inflammatory (PIC) and non-inflammatory (NIC) compounds. Microarraray comparative analysis allowed us to generate a panel of 20 genes that were consistently deregulated by all PICs compared to NICs, thus distinguishing between these two groups. Vk2/E6E7 cells were treated with non-inflammatory compounds: carboxymethyl cellulose (9 samples), hydroxyethyl cellulose (9 samples), pro-inflammatory compounds: imiquimod (6 samples), macrophage activating lipopeptide 2 (MALP2) (6 samples), nonoxynol 9 (N9) (9 samples), Pam3CSK4 (6 arrays), TNF-alpha (6 samples). Non-treated cells (GM) were used as controls (54 samples). Altogether 105 samples were analyzed.