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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:22

Enthalten in:

International journal of molecular sciences - 22(2021), 4 vom: 05. Feb.

Sprache:

Englisch

Beteiligte Personen:

Grabarek, Beniamin Oskar [VerfasserIn]
Kasela, Tomasz [VerfasserIn]
Adwent, Iwona [VerfasserIn]
Zawidlak-Węgrzyńska, Barbara [VerfasserIn]
Brus, Ryszard [VerfasserIn]

Links:

Volltext

Themen:

Adalimumab
Anti-Inflammatory Agents
Caspases
EC 3.4.22.-
Evaluation Study
FYS6T7F842
Journal Article
Keratinocytes
LEP protein, human
LEPR protein, human
Leptin
Lipopolysaccharide A
Lipopolysaccharides
MRNA
RNA, Messenger
RNA, Small Interfering
Receptors, Leptin
SiRNA
Signaling pathway
TNF protein, human
Tumor Necrosis Factor Inhibitors
Tumor Necrosis Factor-alpha

Anmerkungen:

Date Completed 06.09.2021

Date Revised 14.12.2021

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms22041595

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM321228189