Effect of inhibition of interleukin-12/23 by ustekinumab on the expression of leptin and leptin receptor in human THP-1 macrophages.

ABSTRACT: Leptin, an adipocyte-derived circulating cytokine that signals nutritional status, may play a role in the development of psoriasis and its associated systemic diseases. Patients with psoriasis have significantly decreased serum leptin levels compared with controls.To investigate the effect of two commonly used anti-psoriatic biologic drugs, adalimumab and ustekinumab, on leptin and leptin receptor expression in human macrophages.THP-1 differentiated macrophages were cultured under the following conditions: (i) untreated control, (ii) adalimumab 5 ?g/mL, (iii) ustekinumab 1 ?g/mL and (iv) ustekinumab 5 ?g/mL. Expression of leptin and leptin receptors were measured using real-time quantitative PCR and immunoblotting techniques.The presence of either adalimumab or ustekinumab in growth medium significantly upregulated expression of leptin receptor in THP-1 human macrophages to 1.98 ± 0.47 and 2.09 ± 0.24, respectively (n = 3, P < 0.01) vs. 1.12 ± 0.19 for untreated control cells. However, only ustekinumab at a concentration of 5 ?g/mL augmented expression of leptin to 1.99 ± 0.56 (n = 3, P < 0.01) vs. control untreated cells.Enhanced leptin and leptin receptor expression in macrophages exposed to therapeutic levels of ustekinumab suggest a novel immunomodulatory mechanism for this biologic drug. Further mechanistic studies may yield targeted treatment using the leptin pathway, which could reduce the common obesity-related complications of psoriasis while alleviating symptoms and improving prognosis.

SUBMITTER: Voloshyna I 

PROVIDER: S-EPMC4685020 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature