Brazilian Journal of Pharmaceutical Sciences (Apr 2019)

Ustekinumab treats psoriasis by suppressing RORC and T-box but its suppression of GATA restrains its efficacy

  • Lun-Fei Liu,
  • Ji-Su Chen,
  • Ji-Yang Shen,
  • Ting-Ting Dou,
  • Jiong Zhou,
  • Sui-Qing Cai,
  • Min Zheng

DOI
https://doi.org/10.1590/s2175-97902018000417349
Journal volume & issue
Vol. 54, no. 4

Abstract

Read online

Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients’ whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.

Keywords