Signaling events leading to the curative effect of cystatin on experimental visceral leishmaniasis: Involvement of ERK1/2, NF-jB and JAK/STAT pathways
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Signaling events leading to the curative effect of cystatin
on experimental visceral leishmaniasis: Involvement of
ERK1/2, NF-jB and JAK/STAT pathways
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| Creator |
Kar, Susanta
Ukil, Anindita Das, Pijush K |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Curative effect of cystatin, a natural cystein protease inhibitor, on experimental visceral
leishmaniasis was associated with strong upregulation of iNOS. The transductional
mechanisms underlying this cellular response was investigated in themurine macrophage
cell line RAW 264.7 and in the BALB/c mouse model of visceral leishmaniasis. Cystatin
synergizes with IFN-c in inducing ERK1/2 phosphorylation and NF-jB DNA-binding activity.
Pretreatment of cells with specific inhibitors of NF-jB or ERK1/2 pathway blocked the
cystatin plus IFN-c-inducible NF-jB activity and markedly reduced the expression of iNOS
at both mRNA and protein levels. Silencing of mitogen- and stress-activated protein kinase
1 significantly reduced cystatin-mediated NF-jB-dependent iNOS gene transcription
suggesting the involvement of mitogen- and stress-activated protein kinase 1 activation in
ERK1/2 signaling. DNA binding as well as silencing experiments revealed the requirement
of IFN-c-mediated JAK-STAT activation even though cystatin did not modulate this
signaling cascade by itself. In the in vivo situation, key steps in the activation cascade of
NF-jB, including nuclear translocation of NF-jB subunits, IjB phosphorylation and IjB
kinase, are all remarkably enhanced in Leishmania-infected mice by cystatin. Understanding
the molecular mechanisms through which cystatin modulates macrophage
effector responses will contribute to better define its potential for macrophage-associated
diseases, in general.
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| Publisher |
John Wiley & Sons
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| Date |
2009
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/159/1/EUROPEAN_JOURNAL_OF_IMMUNOLOGY%2C39(3)%2C_741%2D751%2C2009[93].pdf
Kar, Susanta and Ukil, Anindita and Das, Pijush K (2009) Signaling events leading to the curative effect of cystatin on experimental visceral leishmaniasis: Involvement of ERK1/2, NF-jB and JAK/STAT pathways. European Journal of Immunology, 39. pp. 741-751. ISSN 0014-2980 |
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| Relation |
http://dx.doi.org/10.1002/eji.200838465
http://www.eprints.iicb.res.in/159/ |
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