Adalimumab Induces a Wound Healing Profile in Patients with Hidradenitis Suppurativa by Regulating Macrophage Differentiation and Matrix Metalloproteinase Expression
| Autor: | Jing Wang, Bohdan P. Harvey, Erin Murphy, Z. Kaymakcalan, Yonghao Cao, Feng Hong, Melanie Ruzek |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lipopolysaccharide Dermatology Matrix metalloproteinase Matrix Metalloproteinase Inhibitors Biochemistry Etanercept 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Adalimumab Medicine Macrophage Humans Hidradenitis suppurativa Molecular Biology Wound Healing business.industry Macrophages Cell Differentiation Cell Biology Tissue inhibitor of metalloproteinase medicine.disease Matrix Metalloproteinases Hidradenitis Suppurativa 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer research Certolizumab Pegol Tumor Necrosis Factor Inhibitors business Wound healing medicine.drug |
| Zdroj: | The Journal of investigative dermatology. 141(11) |
| ISSN: | 1523-1747 |
| Popis: | Adalimumab (ADA) is the only Food and Drug Administration‒approved treatment for moderate-to-severe hidradenitis suppurativa, whereas etanercept and certolizumab-pegol have been shown to be ineffective, suggesting that the mechanism of action of ADA is distinct in hidradenitis suppurativa and may contribute to improved wound healing. Given that macrophages (Mϕs) play pivotal roles throughout the wound healing process, an in vitro Mϕ differentiation assay was carried out to assess the impact of TNF‒anti-TNF complexes on these cells. TNF‒ADA complexes exhibited stronger inhibitory effects on inflammatory Mϕ differentiation. Moreover, RNA sequencing revealed several unique wound healing profiles for TNF‒ADA‒treated inflammatory Mϕs, which were not observed for those treated with either TNF‒etanercept or TNF‒certolizumab-pegol complexes, including the inhibition of the matrix metalloproteinase (MMP) pathway. In addition, ADA administration was found to significantly reduce the levels of inflammatory MMP-1 and MMP-9 while promoting wound-healing MMP-13 and tissue inhibitor of metalloproteinases 2 levels in the circulation of the patients with hidradenitis suppurativa who responded to treatment. Our in vitro findings show that TNF‒ADA‒treated inflammatory Mϕs exhibit a distinct profile resembling wound healing. Moreover, ADA not only differentially regulates MMP expression in patients with hidradenitis suppurativa responding to the therapy but also potentially induces a transition to a profile suggestive of wound healing. |
| Databáze: | OpenAIRE |
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