Indirect Regulation and Equilibrium of p35 and p40 Subunits of Interleukin (IL)-12/23 by Ustekinumab in Psoriasis Treatment
| Autor: | Ji-Su Chen, Ji-Yang Shen, Lun-Fei Liu, Ting-Ting Dou, Jiong Zhou, Sui-Qing Cai, Min Zheng |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 030204 cardiovascular system & hematology Pharmacology Placebo Severity of Illness Index Interleukin-12 Subunit p35 Pathogenesis 03 medical and health sciences 0302 clinical medicine Double-Blind Method Downregulation and upregulation Clinical Research Psoriasis Ustekinumab Humans Medicine RNA Messenger Messenger RNA Interleukin-12 Subunit p40 business.industry Antibodies Monoclonal Interleukin hemic and immune systems General Medicine Middle Aged medicine.disease 030220 oncology & carcinogenesis Interleukin 12 Female Dermatologic Agents business medicine.drug |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 |
| Popis: | BACKGROUND Ustekinumab, a human-derived monoclonal antibody that targets the p40 subunit of interleukin (IL)-12 and IL-23, has excellent clinical efficacy and safety in treating psoriasis, with a long half-life. However, no reports have described the use of human skin/serum samples to elucidate its molecular mechanisms. MATERIAL AND METHODS Twenty-four psoriasis patients were enrolled in our double-blind study and randomly divided into placebo and ustekinumab-administered groups. Dynamic changes in psoriasis area-severity index scores, and mRNA and protein levels of p35 and p40 were analyzed at 3 time points (before treatment and during the 12th and 24th weeks of treatment). RESULTS Ustekinumab initially increased and then decreased p35 mRNA expression, but increased p40 mRNA levels throughout the study. The p35 protein levels were not significantly altered, while p40 protein levels were increased after the first 2 injections but decreased after the third injection. CONCLUSIONS We concluded that 2 equilibria influence the efficacy of ustekinumab against psoriasis. First, because of the dual roles of p35 in psoriasis pathogenesis, homeostasis occurs between p35 and p40 expression levels. The second balance lies between the upregulation of p40 mRNA levels and the ability of ustekinumab to neutralize the function of the elevated p40 protein. |
| Databáze: | OpenAIRE |
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