Effective therapy with anti-TNF-α in patients with psoriatic arthritis is associated with decreased levels of metalloproteinases and angiogenic cytokines in the sera and skin lesions

Paola Cordiali-Fei, Elisabetta Trento, Giovanna D'Agosto, Valentina Bordignon, Anna Mussi, Marco Ardigò, Antonio Mastroianni, Antonella Vento, Francesco Solivetti, Enzo Berardesca, Fabrizio Ensoli

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Tumor necrosis factor-α (TNF-α) plays a central role in sustaining the inflammatory process in the skin as well as in the joints of patients with psoriasis and psoriatic arthritis. In fact, biological therapies based on monoclonal antibodies against TNF-α have been proven to be effective on both the arthropathy and the cutaneous symptoms of the disease. Among the several effects produced by TNF-α on keratinocytes there is the induction of expression of MMP-9,a matrix metalloproteinase (MMP) produced mainly by monocytes and macrophages. In this article we refer to the results of a study on the behavior of MMP-9 in the sera and in the lesional skin in association with effective therapy with infliximab. Measurements of TNF-α, MMP-2, vascular endothelial growth factor (VEGF), and E-selectin were also performed in the same samples. Eleven psoriatic patients included in a therapeutic protocol based on the administration of infliximab monotherapy were collected before treatment and after 6 and 12 weeks of therapy. Significant decrease of MMP-9 and MMP-2 levels in the sera was associated with clinical improvement and with the decrease of TNF-α, VEGF, and E-selectin, angiogenic molecules already known to be implicated in the clinical expression of psoriasis. The clinical amelioration of the cutaneous expression of psoriasis was significantly associated with the decrease of MMP-9, TNF-α, and E-selectin levels, spontaneously released by lesional biopsy samples before and after therapy, measured in the culture supernatants by immunoenzymatic assays. In addition, significant correlations were found between the clinical score and TNF-α, MMP-9, and E-selectin lesional production. MMP-9 levels were significantly correlated with those of TNF-α. Our findings show the existence of a direct relationship between MMP-9 and TNF-α production, strongly suggesting that MMP-9 may play a key role in the skin inflammatory process in psoriasis, while a different role may be attributed to MMP-2.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages578-589
Number of pages12
Volume1110
DOIs
Publication statusPublished - Sep 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1110
ISSN (Print)00778923
ISSN (Electronic)17496632

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Keywords

  • Infliximab
  • Lesional cytokines
  • MMP-2
  • MMP-9
  • Psoriasis
  • TNF-α

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cordiali-Fei, P., Trento, E., D'Agosto, G., Bordignon, V., Mussi, A., Ardigò, M., Mastroianni, A., Vento, A., Solivetti, F., Berardesca, E., & Ensoli, F. (2007). Effective therapy with anti-TNF-α in patients with psoriatic arthritis is associated with decreased levels of metalloproteinases and angiogenic cytokines in the sera and skin lesions. In Annals of the New York Academy of Sciences (Vol. 1110, pp. 578-589). (Annals of the New York Academy of Sciences; Vol. 1110). https://doi.org/10.1196/annals.1423.062