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Plasmin plays an essential role in amplification of psoriasiform skin inflammation in mice. PLoS One 2011 Feb 02;6(2):e16483

Date

02/12/2011

Pubmed ID

21311769

Pubmed Central ID

PMC3032787

DOI

10.1371/journal.pone.0016483

Scopus ID

2-s2.0-79551642928 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

BACKGROUND: Although increased levels of plasminogen activators have been found in psoriatic lesions, the role of plasmin converted from plasminogen by plasminogen activators in pathogenesis of psoriasis has not been investigated.

METHODOLOGY/PRINCIPAL FINDINGS: Here we examined the contribution of plasmin to amplification of inflammation in patients with psoriasis. We found that plasminogen was diminished, but that the amount and activity of its converted product plasmin were markedly increased in psoriasis. Moreover, annexin II, a receptor for plasmin was dramatically increased in both dermis and epidermis in psoriasis. Plasmin at sites of inflammation was pro-inflammatory, eliciting production of inflammatory factors, including CC chemokine ligand 20 (CCL20) and interleukin-23 (IL-23), that was mediated by the nuclear factor-kappaB (NF-κB) signaling pathway and that had an essential role in the recruitment and activation of pathogenic C-C chemokine receptor type 6 (CCR6)+ T cells. Moreover, intradermal injection of plasmin or plasmin together with recombinant monocyte/macrophage chemotactic protein-1 (MCP-1) resulted in induction of psoriasiform skin inflammation around the injection sites with several aspects of human psoriasis in mice.

CONCLUSIONS/SIGNIFICANCE: Plasmin converted from plasminogen by plasminogen activators plays an essential role in amplification of psoriasiform skin inflammation in mice, and targeting plasmin receptor--annexin II--may harbor therapeutic potential for the treatment of human psoriasis.

Author List

Li Q, Ke F, Zhang W, Shen X, Xu Q, Wang H, Yu XZ, Leng Q, Wang H

Author

Xue-Zhong Yu MD Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Case-Control Studies
Cells, Cultured
Chemokine CCL20
Disease Progression
Ear
Female
Fibrinolysin
Humans
Inflammation
Interleukin-23
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B
Plasminogen
Psoriasis
Receptors, CCR6
Skin Diseases
T-Lymphocytes