Cystatin cures visceral leishmaniasis by NF-jBmediated proinflammatory response through co-ordination of TLR/MyD88 signaling with p105-Tpl2-ERK pathway
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Cystatin cures visceral leishmaniasis by NF-jBmediated
proinflammatory response through
co-ordination of TLR/MyD88 signaling
with p105-Tpl2-ERK pathway
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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 |
Cystatin could completely cure experimental visceral leishmaniasis by switching the
differentiation of Th2 cells to Th1 type, as well as upregulating NO, and activation of NF-jB
played a major role in these processes. Analysis of upstream signaling events revealed
that TLR 2/4-mediated MyD88-dependent participation of IL-1R-activated kinase (IRAK)1,
TNF receptor-associated factor (TRAF)6 and TGFb-activated kinase (TAK)1 is essential to
induce cystatin-mediated IjB kinase (IKK)/NF-jB activation in macrophages. Cystatin plus
IFN-c activated the IKK complex to induce phosphorylation-mediated degradation of p105,
the physiological partner and inhibitor of the MEK kinase, tumor progression locus 2 (Tpl-
2). Consequently, Tpl-2 was liberated from p105, thereby stimulating activation of the
MEK/ERK MAPK cascade. Cystatin plus IFN-c-induced IKK-b post-transcriptionally modi-
fied p65/RelA subunit of NF-jB by dual phosphorylation in infected phagocytic cells. IKK
induced the phosphorylation of p65 directly on Ser-536 residue whereas phosphorylation
on Ser 276 residue was by sequential activation of Tpl-2/MEK/ERK/MSK1. Collectively, the
present study indicates that cystatin plus IFN-c-induced MyD88 signaling may bifurcate at
the level of IKK, leading to a divergent pathway regulating NF-jB activation by IjBa
phosphorylation and by p65 transactivation through Tpl-2/MEK/ERK/MSK1.
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| Date |
2011
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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/53/1/EUROPEAN_JOURNAL_OF_IMMUNOLOGY_41(1)%2C116%2D127%2C2011[109].pdf
Kar, Susanta and Ukil, Anindita and Das, Pijush K (2011) Cystatin cures visceral leishmaniasis by NF-jBmediated proinflammatory response through co-ordination of TLR/MyD88 signaling with p105-Tpl2-ERK pathway. Eur. Journal Of Immunology, 41 (1). |
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| Relation |
http://dx.doi.org/10.1002/eji.201040533
http://www.eprints.iicb.res.in/53/ |
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