Anti-TNF-α monoclonal antibody reverses psoriasis through dual inhibition of inflammation and angiogenesis.
Int Immunopharmacol
; 28(1): 731-43, 2015 Sep.
Article
de En
| MEDLINE
| ID: mdl-26263167
ABSTRACT
Tumor necrosis factor-alpha (TNF-α) antagonists have shown remarkable efficacy in psoriasis; however, the precise mechanisms of action of TNF-α blocking agents mainly focus on their neutralizing TNF-α and its anti-inflammatory effects. In this study, we generated a humanized anti-TNF-α monoclonal antibody (IBI303) and suggested a potential mechanism of anti-TNF-α therapy for psoriasis. The results of SPR and ELISA indicated that IBI303 has a good affinity to TNF-α. In vitro, it could suppress TNF-α-induced cytotoxicity in WEHI164 cells. In vivo, administration of IBI303 to K14-VEGF transgenic mice led to a significant treatment efficiency in psoriasis in a dose-dependent manner. IHC staining and cytokines-ELISA indicated that TNF-α inhibition strongly reduced inflammatory cells infiltration and pro-inflammatory cytokines release, accompanied by suppression of inflamed dermal blood vessels. Mechanistically, in order to explain the anti-angiogenesis effect of anti-TNF-α antibody, the production of cytokine in macrophage conditional medium was measured by ELISA. The result indicated that the massive secretion of TNF-α stimulated by LPS in RAW264.7 cell supernatant was markedly neutralized in a dose-response manner by IBI303, moreover, the expression of NF-κB p65 was down-regulated. Mouse endothelial cell tube formation assay showed that anti-TNF-α could inhibit blood vessels formation directly and indirectly. Collectively, our study suggested a kind of antipsoriatic mechanism of TNF-α inhibitors that is the dual inhibition of inflammation and angiogenesis.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Psoriasis
/
Facteur de nécrose tumorale alpha
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Néovascularisation physiologique
/
Inhibiteurs de l'angiogenèse
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Anticorps monoclonaux humanisés
/
Anti-inflammatoires
Limites:
Animals
Langue:
En
Journal:
Int Immunopharmacol
Sujet du journal:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Année:
2015
Type de document:
Article