Modification of osteopontin and MMP-9 levels in patients with psoriasis on anti-TNF-α therapy.
Gaudiello, Francesca (2011) Modification of osteopontin and MMP-9 levels in patients with psoriasis on anti-TNF-α therapy. [Tesi di dottorato] (Inedito)
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Osteopontin (OPN) an aspartic acid-rich, N-linked glycosylated protein, is a secreted adhesive molecule, and it is thought to aid in the recruitment of monocytes-macrophages and to regulate cytokine production in macrophages, dendritic cells, and T-cells. Psoriasis is an immune-mediated inflammatory disorder, where Th1 and Th17 lymphocytes contribute to the pathogenesis through the release of inflammatory cytokines that promote further recruitment of immune cells, keratinocyte proliferation and sustained inflammation. Tumor necrosis factor alpha (TNF-α) is a pleiotropic cytokine with a central role in the pathogenesis of psoriasis. Among the multiple effects produced by TNF-α on keratinocytes, the induction of matrix metalloproteinase 9 (MMP-9) a collagenase implicated in psoriasis, might represent a key mechanism in the pathogenesis of the disease. Biological therapy based on monoclonal antibodies against TNF-α has been proven to be effective in patients with psoriasis. Aim of the present study was to investigate the relationship between OPN, MMP-9 and TNF-α in psoriasis, by assessing the presence of OPN and MMP-9 in PBMC and sera of 7 psoriatic patients before and after anti-TNF-α treatment. We demonstrated that TNF-α antagonists (etanercept and adalimumab) were able to decrease OPN either in PBMC or in plasma. Our findings showed also anti TNF-α treatment reduced also MMP-9 expression in PBMC of psoriatic patients.
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