Evaluation of the Influence of Adalimumab on the Expression Profile of Leptin-Related Genes and Proteins in Keratinocytes Treated with Lipopolysaccharide A

Abstract

Psoriasis is a disease with a proinflammatory base, in which an increased expression of leptin, tumor necrosis factor alpha (TNF-α), interleukin (IL) IL-12/23, IL-6, is observed. A drug used in the treatment of psoriasis of moderate and acute strength is the monoclonal antibody anti-TNF–adalimumab. The goal of this study was to evaluate the influence of adalimumab on changes in the expression profile of leptin-related genes in human keratinocyte cells exposed to lipopolysaccharide A and analyze if adalimumab acts via leptin pathways. The evaluation of changes of the pattern of genes connected with leptin and proteins coded by them was marked in a culture of human keratinocytes (HaCaT) exposed to 1 µg/mL lipopolysaccharide A (LPS) for 8 h in order to induce the inflammatory process, then to 8 µg/mL of adalimumab for 2.8 and 24 h in comparison with the control (cells not treated with the substances). The techniques used were mRNA microarray, Real-Time Quantitative Reverse Transcription Reaction (RTqPCR), Enzyme-Linked Immunosorbent Assay (ELISA), as well as transfections of HaCaT culture with leptin small interfering RNA (siRNA) in order to see whether adalimumab works through pathways dependent on leptin. A statistically lower expression of leptin and its receptors was observed under the influence of the drug, independent of the exposition time of keratinocytes to adalimumab. In the cells transfected with leptin siRNA, a lower concentration of JAK2 and STAT3 proteins was observed, which confirms that adalimumab works through pathways dependent on leptin. Adalimumab has a modulatory effect on the gene expression pattern and the proteins coded by them connected with leptin in keratinocytes treated with LPS in vitro.

Adiponectin and Leptin Exert Antagonizing Effects on HUVEC Tube Formation and Migration Modulating the Expression of CXCL1, VEGF, MMP-2 and MMP-9

“…We first confirmed the presence of adiponectin receptors on HUVEC endothelial cells by real time PCR and found the expression of AdipoR1, AdipoR2 and T-cadherin ( Figure 1 , panel A). The expression of the Leptin receptor, OB-R, has been previously demonstrated [ 29 , 30 , 31 ].…”

Delanzomib, a Novel Proteasome Inhibitor, Combined With Adalimumab Drastically Ameliorates Collagen-Induced Arthritis in Rats by Improving and Prolonging the Anti-TNF-α Effect of Adalimumab

“…For this reason, delanzomib may be available for the treatment of some systemic autoimmune diseases including RA, psoriasis vulgaris, atopic dermatitis, and so on, where TNF-α plays an important role in the pathophysiology. On the other hand, adalimumab is a widely used monoclonal antibody that targets against the proinflammatory cytokine TNF-α or affects the expression profiles of genes involved in the pathophysiology of diseases for the treatment of inflammatory and autoimmune diseases including RA and psoriasis ( Bang and Keating, 2004 ; Fleischmann et al, 2019 ; Grabarek et al, 2019 ; Grabarek et al, 2021 ). TNF-α was eliminated by binding to adalimumab to trigger antibody-dependent cellular cytotoxicity or complement activation ( Bang and Keating, 2004 ).…”

“…While working on the same target TNF-α, delanzomib may exert a synergistic effect with other anti-TNF-α therapeutic proteins on the pathophysiology of RA ( Xi et al, 2019 ). Adalimumab is a widely used anti-TNF-α therapeutic protein for the treatment of RA and psoriasis by neutralizing TNF-α or by affecting the expression profiles of genes involved in the pathophysiology of diseases ( Wcisło-Dziadecka et al, 2018 ; Grabarek et al, 2019 ; Grabarek et al, 2021 ). Whether delanzomib can be used for the treatment of RA and whether pharmacodynamics interactions exist between delanzomib and adalimumab needs further exploration.…”

Effects of Cyclosporine A and Adalimumab on the expression profiles histaminergic system-associated genes and microRNAs regulating these genes in HaCaT cells

“…HaCaT cells (CLS Cell Lines Service, Eppelheim, Germany) were cultured in Dulbecco’s modified Eagle’s medium (Sigma-Aldrich, St. Louis, MO, USA) supplemented with 4500 mg/L glucose (Sigma-Aldrich), 10% fetal bovine serum (Sigma-Aldrich), 100 U/mL penicillin (Sigma-Aldrich), 100 mg/mL streptomycin (Sigma-Aldrich), and 2 mM glutamine (Sigma-Aldrich) at 37°C and 5% CO 2 . Based on our previous studies [ 15–17 ], HaCaT cells were incubated with 1 μg/mL LPS for 8 h, followed by incubation with 8 μg/mL adalimumab or 100 ng/mL of CSA for 2 (H_2 group), 8 (H_8 group), or 24 h (H_24 group). HaCaT cells not treated with LPS, adalimumab, or CSA served as controls.…”

“…Previously, we had demonstrated the effect of adalimumab and cyclosporine A (CSA) on the transcriptome and proteome of the human adult, low-calcium, high-temperature, keratinocytes (HaCaT) [ 15–18 ].…”