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Effect of inhibition of interleukin‐12/23 by ustekinumab on the expression of leptin and leptin receptor in human THP ‐1 macrophages
Author(s) -
Voloshyna I.,
Mounessa J.,
Carsons S. E.,
Reiss A. B.
Publication year - 2016
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/ced.12699
Subject(s) - ustekinumab , leptin , medicine , leptin receptor , endocrinology , adipokine , adalimumab , cytokine , psoriasis , receptor , immunology , tumor necrosis factor alpha , obesity
Summary Background 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. Aim To investigate the effect of two commonly used anti‐psoriatic biologic drugs, adalimumab and ustekinumab, on leptin and leptin receptor expression in human macrophages. Methods THP ‐1 differentiated macrophages were cultured under the following conditions: (i) untreated control, (ii) adalimumab 5 μg/ mL , (iii) ustekinumab 1 μg/ mL and (iv) ustekinumab 5 μg/ mL . Expression of leptin and leptin receptors were measured using real‐time quantitative PCR and immunoblotting techniques. Results 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 μg/mL augmented expression of leptin to 1.99 ± 0.56 ( n = 3, P < 0.01) vs. control untreated cells. Conclusions 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.