Possible Interaction: Tretinoin and Sirolimus

“However, combined use of rapamycin and all-trans retinoic acid abolishes IL-17 production and confers a specific chemokine receptor homing profile upon regulatory T cells.”

“The enhancing effects of retinoids on the proliferative response of PMA-stimulated PBMCs were reversed by rapamycin (10 ng/ml), an immunosuppressant known to inhibit the phorbol ester-induced protein kinase C pathway of lymphocyte activation.”

“ ATRA activated p70S6k1 in MSCs in vitro, which was completely inhibited by rapamycin.”

“Based on our data, translational studies could confirm whether combination of RA with reduced dosage of rapamycin would have more beneficial effects to higher dosage of rapamycin monotherapy meanwhile reducing adverse effects of rapamycin for patients with TSC mutation.”

“Results:Ex-vivo … of TRA significantly induced the expression of a4b7 compared to Rapamycin alone (5.57%±3.12 vs …=0.0057) Cells treated with Rapa+ATRA maintained their superior suppressive ability compared to R apamycin treated Tregs (95.8%±3.5% vs 91.…; at Treg:Teff 1:1 ratio).”

“To conclude, (i) pharmacological characterization of PI3K-Akt-mTOR inhibitors requires carefully standardized experimental models, (ii) rapamycin effects differ … patients, and (iii) combined targeting of different steps in this pathway should be further investigated whereas combination of rapamycin with valproic acid, ATRA , or NF-κB inhibitors seems less promising.”