Interleukin-8 induces CYP26A1 expression by enhancing transcription of the HOXA10v2 factor. (A) Transcription of the HOXA10v2 factor following the administration of proteins secreted into the culture medium by differentiated NB4 cells (Diff Prot). Results following the administration of proteins secreted by untreated NB4 cells (UnT Prot). HOXA10v2 induction with fractions obtained by the size exclusion liquid chromatography of Diff Prot (Diff Prot fractions). Elutions were evaluated by transferring onto nitrocellulose membranes, staining with red Ponceau, and testing with the human IL-8 enzyme immunosorbent assay (cupules) prior to their administration to proliferative NB4 cells for 12 hours. (B) Results following protein inactivation by boiling the protein extract for 15 minutes at 100°C (Δ Diff Prot) or following the earlier inhibition of the IL-8 receptor (CXCR2) with 200 nM of the SB225002 antagonist (CXCR2 inh + Diff Prot). Results following the addition of 25 ng/mL recombinant interleukin-8 (rIL-8). Because CYP26A1 expression required the activation of the retinoid signal, NB4 cells were treated with ATRA (0.1 μM), either with the previous inhibition of the IL-8 signal with 200 nM of the SB225 002 antagonist (ATRA + CXCR2 inh) or following the addition of rIL-8 at a final dose of 25 ng/mL (ATRA + rIL-8). (C) Results of the CYP26A1 transcriptional modulation measured by real-time PCR. *P < .05 compared with ATRA control. The specificity of the enhancement of CYP26A1 transcription was verified by measuring the modulation of other retinoid-induced targets (cumulative means for HIC1, PRAM1, and CEBPB). Error bars represent the standard error (n = 3).