Etanercept ameliorates psoriasis progression through regulating high mobility group box 1 pathway

Abstract

Background As a common skin disease, psoriasis is related to inflammation and immune response. Due to the frequent recurrence of psoriasis, the treatment of psoriasis remains a clinical challenge. As an effective tumor necrosis factor‐alpha (TNF‐α) inhibitor, etanercept has been used for the treatment of psoriasis. However, some patients with psoriasis have no response to etanercept or discontinue treatment. To improve the therapeutic effect of etanercept, searching the potential biomarkers and investigating the related mechanisms of etanercept in the treatment of psoriasis are vital. Materials and methods We stimulated HaCaT cells with lipopolysaccharide (LPS) to generate cellular psoriatic changes and established an imiquimod (IMQ)‐induced psoriasis‐like mouse model, and then used an etanercept to treat cell and mouse model. Results Etanercept alleviated IMQ‐induced pathological changes and inflammation, and it also decreased the protein expression of high mobility group box 1 (HMGB1), receptor for advanced glycation end‐products, and toll‐like receptor 4. Moreover, the results of in vitro experiments showed that etanercept inhibited proliferation and inflammation, and promoted cell cycle arrest and apoptosis in LPS‐treated HaCaT cells. Knockdown of HMGB1 further enhanced the inhibitory effects of etanercept on LPS‐treated HaCaT cell viability and inflammation, while overexpression of HMGB1 notably reversed the inhibitory effects of etanercept on LPS‐induced HaCaT cell viability and inflammation. Conclusion Etanercept inhibited proliferation and inflammation and promoted cell cycle arrest and apoptosis in LPS‐induced HaCaT cells, and etanercept ameliorated inflammation in a psoriasis‐like mouse model.

Cosentyx alleviates psoriasis‐induced podocyte injury by inhibiting the tlr/nf‐κb signaling pathway

“…31 In line with our findings, existing literature suggests that Etanercept alleviates IMQ-induced pathological changes and inflammation, reduces the protein expression of High Mobility Group Box 1 (HMGB1), receptor for advanced glycation end-products, and Toll-like receptor 4, ultimately improving inflammation in a psoriasis-like mouse model. 32 Through a comprehensive analysis of these research outcomes, a deeper understanding of the intricate nature of psoriasis is attained, offering more precise directions for future research and treatment strategies.…”

The Role of Alarmins in the Pathogenesis of Rheumatoid Arthritis, Osteoarthritis, and Psoriasis

“…Overexpression of HMGB1 attenuated the inhibitory effect of etanercept. Mechanistically, TNF-α causes HMGB1 translocation to the cytoplasm, which, as mentioned before, is a signal for its secretion, enabling this alarmin to exert immune effects [170]. One study examined the level of alarmins after anti-psoriatic therapy in pediatric patients who underwent the Goeckerman regimen (GR), which consists of applying pharmaceutical crude tar and UVB light exposure.…”

Paradoxical and bimodal immune‐mediated dermatological side effects of TNF‐α inhibitors: A comprehensive review

“…Additionally, this class of drugs can reduce the expression of high mobility group box 1 (HMGB1), thereby reducing inflammation. 2,4,5 In some diseases, such as psoriasis and rheumatoid arthritis, these drugs are approved by the FDA; in others, such as pyoderma gangrenosum and juvenile idiopathic arthritis, they are used off-label. 4 Gradually, it became clear that TNF-α inhibitors can paradoxically cause the same diseases they treat.…”