moDC chemokine suppression by SFA is independent of cylophilin A binding.

<p>To analyze whether DC chemokine suppression by SFA is dependent on cyclophilin A binding competitive experiments with a 100-fold molar excess of CsA (A) and with a 10-fold molar excess of a cyclophilin-binding nonimmunosuppressive derivative of CsA, 4_Cs (B) were performed. 4-Cs has been reported to efficiently inhibit SFA cyclophilin A binding <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018406#pone.0018406-Zenke1" target="_blank">[5]</a>. Human moDC were pre-exposed to 10 µM CSA and 1 hour later to 100 nM SFA (A). With respect to 4-Cs, moDC were pre-exposed to 2500 nM 4-Cs and 1 hour later to 250 nM SFA (B). After 4 hours, moDCs were stimulated with LPS (100 ng/ml) and DC chemokine production were analyzed after 12 h by ELISA. In the presence of a 100-fold molar excess of CsA or a 10-fold molar excess of 4-Cs, SFA's DC chemokine inhibitory activity was not abrogated. In contrast, 10 µM CSA did not inhibit CCL5 (F) or CCL17 (G) moDC production and only moderately inhibited CCL19 (H) expression. 4-Cs did not inhibit CCL5, CCL17 or CCL19 production. Mean (± SEM) of n = 3–6 independent experiments. **p<0.01, *p<0.05 versus vehicle.