PMID- 23381993
OWN - NLM
STAT- MEDLINE
DCOM- 20130514
LR  - 20211021
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 81
IP  - 4
DP  - 2013 Apr
TI  - 5-Lipoxygenase activity increases susceptibility to experimental Paracoccidioides 
      brasiliensis infection.
PG  - 1256-66
LID - 10.1128/IAI.01209-12 [doi]
AB  - Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the thermodimorphic 
      fungus Paracoccidioides brasiliensis. Leukotrienes and lipoxins are lipid 
      mediators produced after 5-lipoxygenase (5-LO) activation that exhibit pro- and 
      anti-inflammatory roles, respectively. Here, we have investigated the 
      contribution of 5-LO enzymatic activity in PCM using an experimental model of P. 
      brasiliensis infection. B6.129 wild-type (B6.129) and 5-LO-deficient (5-LO(-/-)) 
      mice were intravenously inoculated with a virulent strain of P. brasiliensis 
      (Pb18), and the survival rate of the infected mice was investigated on different 
      days after yeast infection. 5-LO(-/-) mice exhibited an increased survival rate 
      associated with a decreased number of CFU. The resistance of 5-LO(-/-) during PCM 
      was associated with augmented nitric oxide (NO) production and the formation of 
      compact granulomas. In addition, the absence of 5-LO was associated with a 
      diminished number of CD4(+) CD25(+) regulatory T cells, higher levels of gamma 
      interferon and interleukin-12, and increased T-bet (a T-box transcription factor 
      that directs Th1 lineage commitment) mRNA levels in the lungs. Taken together, 
      our results show for the first time that 5-LO enzymatic activity increases 
      susceptibility to P. brasiliensis, suggesting that this pathway may be a 
      potential target for therapeutic intervention during PCM.
FAU - Tristao, Fabrine Sales Massafera
AU  - Tristao FS
AD  - Departamento de Bioquimica e Imunologia, Universidade de Sao Paulo, Ribeirao 
      Preto, Sao Paulo, Brazil.
FAU - Rocha, Fernanda Agostini
AU  - Rocha FA
FAU - Moreira, Ana Paula
AU  - Moreira AP
FAU - Cunha, Fernando Queiroz
AU  - Cunha FQ
FAU - Rossi, Marcos Antonio
AU  - Rossi MA
FAU - Silva, Joao Santana
AU  - Silva JS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130204
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (T-box transcription factor TBX21)
RN  - 187348-17-0 (Interleukin-12)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
SB  - IM
MH  - Animals
MH  - Arachidonate 5-Lipoxygenase/deficiency/*metabolism
MH  - Colony Count, Microbial
MH  - Disease Models, Animal
MH  - Gene Expression Profiling
MH  - Granuloma/microbiology/pathology
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-12/biosynthesis
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Nitric Oxide/metabolism
MH  - Paracoccidioides/*pathogenicity
MH  - Paracoccidioidomycosis/*microbiology/*mortality/pathology
MH  - Survival Analysis
MH  - T-Box Domain Proteins/biosynthesis
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Time Factors
PMC - PMC3639621
EDAT- 2013/02/06 06:00
MHDA- 2013/05/15 06:00
PMCR- 2013/10/01
CRDT- 2013/02/06 06:00
PHST- 2013/02/06 06:00 [entrez]
PHST- 2013/02/06 06:00 [pubmed]
PHST- 2013/05/15 06:00 [medline]
PHST- 2013/10/01 00:00 [pmc-release]
AID - IAI.01209-12 [pii]
AID - 01209-12 [pii]
AID - 10.1128/IAI.01209-12 [doi]
PST - ppublish
SO  - Infect Immun. 2013 Apr;81(4):1256-66. doi: 10.1128/IAI.01209-12. Epub 2013 Feb 4.