PMID- 21311769
OWN - NLM
STAT- MEDLINE
DCOM- 20110901
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 2
DP  - 2011 Feb 2
TI  - Plasmin plays an essential role in amplification of psoriasiform skin 
      inflammation in mice.
PG  - e16483
LID - 10.1371/journal.pone.0016483 [doi]
LID - e16483
AB  - 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-kappaB) 
      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.
FAU - Li, Qun
AU  - Li Q
AD  - Department of Hypertension of Shanghai Ruijin Hospital, Shanghai Institute of 
      Hypertension and Institute of Health Sciences, Shanghai Jiao Tong University 
      School of Medicine and Shanghai Institutes for Biological Sciences, Chinese 
      Academy of Sciences, Shanghai, China.
FAU - Ke, Fang
AU  - Ke F
FAU - Zhang, Weiwei
AU  - Zhang W
FAU - Shen, Xiaoyan
AU  - Shen X
FAU - Xu, Qiannan
AU  - Xu Q
FAU - Wang, Hong
AU  - Wang H
FAU - Yu, Xue-Zhong
AU  - Yu XZ
FAU - Leng, Qibin
AU  - Leng Q
FAU - Wang, Honglin
AU  - Wang H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110202
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CCR6 protein, mouse)
RN  - 0 (Chemokine CCL20)
RN  - 0 (Interleukin-23)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, CCR6)
RN  - 9001-91-6 (Plasminogen)
RN  - EC 3.4.21.7 (Fibrinolysin)
SB  - IM
MH  - Animals
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Chemokine CCL20/genetics/metabolism
MH  - Disease Progression
MH  - Ear/pathology
MH  - Female
MH  - Fibrinolysin/genetics/metabolism/*physiology
MH  - Humans
MH  - Inflammation/complications/genetics/immunology/*pathology
MH  - Interleukin-23/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism/physiology
MH  - Plasminogen/genetics/metabolism
MH  - Psoriasis/complications/genetics/immunology/*pathology
MH  - Receptors, CCR6/genetics/metabolism
MH  - Skin Diseases/complications/genetics/immunology/*pathology
MH  - T-Lymphocytes/immunology/metabolism
PMC - PMC3032787
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/02/12 06:00
MHDA- 2011/09/02 06:00
PMCR- 2011/02/02
CRDT- 2011/02/12 06:00
PHST- 2010/10/04 00:00 [received]
PHST- 2010/12/22 00:00 [accepted]
PHST- 2011/02/12 06:00 [entrez]
PHST- 2011/02/12 06:00 [pubmed]
PHST- 2011/09/02 06:00 [medline]
PHST- 2011/02/02 00:00 [pmc-release]
AID - PONE-D-10-02924 [pii]
AID - 10.1371/journal.pone.0016483 [doi]
PST - epublish
SO  - PLoS One. 2011 Feb 2;6(2):e16483. doi: 10.1371/journal.pone.0016483.