Effect of inhibition of interleukin‐12/23 by ustekinumab on the expression of leptin and leptin receptor in human THP‐1 macrophages
I Voloshyna, J Mounessa, SE Carsons… - Clinical and …, 2016 - academic.oup.com
I Voloshyna, J Mounessa, SE Carsons, AB Reiss
Clinical and experimental dermatology, 2016•academic.oup.comBackground 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 …
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 …
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.
Oxford University Press