Etanercept Improves Psoriasis Progression

In a cell and mouse model, tumor necrosis factor-alpha (TNF-α) inhibitor etanercept improved pathological changes and progression of psoriasis.

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In a recent study,¹ researchers sought to contribute to the therapeutic improvement of etanercept in psoriasis treatment by investigating its related mechanisms and the disease’s potential biomarkers.

Researchers first obtained HaCaT cells. These cells were first cultured and then supplemented with 10% fetal bovine serum and 1% penicillin and streptomycin. Then, the cells were starved for a 12-hour period prior to treatment and transfection in a serum-free environment.

After this, researchers exposed the HaCaT cells to varying doses of etanercept in a controlled temperature CO2 environment. These doses were 0, 5, 10, 20, 40, and 80 μg/ml.

Before dividing cells into various groups (control and research), researchers constructed hyperproliferative psoriatic keratinocytes utilizing lipopolysaccharide (LPS). The study groups were as follows:

• Control group: HaCaT cells without treatment
• LPS
• LPS+5 μg/ml Etanercept
• LPS + 40 μg/ml Etanercept
• LPS+Etanercept+si-high mobility box group 1 (HMGB1)
• LPS+Etanercept+HMGB1

Additionally, researchers conducted a cell viability assay, 5-ethynyl-2'-deoxyurdine assay, cell cycle analysis, apoptosis assay, Western blot analysis, reverse transcription-quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay.

Next, researchers conducted an imiquimod (IMQ)-induced psoriasis mouse model. Researchers randomized mice into 4 groups: control, model, model+methotrexate(MTX), and model+etanercept, with 8 mice assigned to each group.

For 8 days, researchers used IMQ cream on the ears of the mice to induce psoriasis on all groups aside from the control group, where a vehicle-control cream was applied instead.

After this, researchers intraperitoneally injected mice in the model+MTX group with 1 mg/kg/dayMTX for 12 days. Mice in the model+etanercept group were intraperitoneally injected with 4 mg/kg etanercept once every 3 days for 12 days.

Following the 12-day period, researchers conducted hematoxylin and eosin (H&E) staining, RT-qPCR, western blot assay, and a subsequent statistical analysis.

As a result of the study, researchers found that etanercept inhibits proliferation in HaCaT cells. Furthermore, it is also capable of inducing cell cycle arrest and apoptosis. It had the same effect in LPS-induced HaCaT cells.

Etanercept also suppressed both inflammation and proliferation in HaCaT cells that were triggered by LPS in the HMGB1 signaling pathway.

“We found that etanercept inhibited proliferation and inflammation, promoted cell cycle arrest and apoptosis in LPS-induced HaCaT cells, and etanercept ameliorated inflammation in an IMQ-induced psoriasis-like mouse model. Moreover, the therapeutic effects of etanercept in psoriasis were related to the HMGB1 signaling pathway,” study authors wrote. “Our findings suggested that etanercept decreased the expression of IL-8, IL-6, and TNF-α, and alleviate IMQ-induced pathological changes. Moreover, the therapeutic effect of etanercept on mice was similar to that of MTX. Taken together, these findings demonstrated that etanercept exerted a therapeutic effect by inhibiting inflammation.”

Reference

1. Li S, Li G, Li X, Wu F, Li L. Etanercept ameliorates psoriasis progression through regulating high mobility group box 1 pathway. Skin Research and Technol. 2023;29(4). doi:10.1111/srt.13329