MAPK-Directed Phosphatases Preferentially Regulate Pro- and Anti-Inflammatory Cytokines in Experimental Visceral leishmaniasis: involvement of distinct protein kinase C isoforms
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
MAPK-Directed Phosphatases Preferentially
Regulate Pro- and Anti-Inflammatory
Cytokines in Experimental Visceral
leishmaniasis: involvement of distinct
protein kinase C isoforms
|
|
| Creator |
Kar, Susanta
Ukil, Anindita Sharma, Gunjan Das, Pijush K |
|
| Subject |
Infectious Diseases and Immunology
|
|
| Description |
The role of phosphatases in the impairment of MAPK
signaling, which is directly responsible for Leishmaniainduced
macrophage dysfunction, is still poorly understood.
Gene expression profiling revealed that Leishmania
donovani infection markedly up-regulated the expression
of three phosphatases: MKP1, MKP3, and PP2A.
Inhibition of these phosphatases prior to infection points
toward preferential induction of the Th2 response
through deactivation of p38 by MKP1. On the other hand,
MKP3 and PP2A might play significant roles in the inhibition
of iNOS expression through deactivation of ERK1/2.
Among various PKC isoforms, PKC� was associated with
induction of MKP3 and PP2A in infected macrophages,
whereas PKC� was correlated with MKP1 induction. Inhibition
of phosphatases in L. donovani-infected BALB/c mice
shifted the cytokine balance in favor of the host by inducing
TNF-� and iNOS expression. This was validated by cystatin,
an immunomodulator and curing agent for experimental
visceral leishmaniasis, which showed that inhibition of
MKPs and PP2A activity may be necessary for a favorable
T cell response and suppression of organ parasite burden.
This study, for the first time, suggests the possibility of the
involvement of MAPK-directed phosphatases in the establishment
of L. donovani infection. J. Leukoc. Biol. 88: 9–20;
2010.
|
|
| Date |
2010
|
|
| Type |
Article
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/73/1/JOURNAL_OF_LEUKOCYTE_BIOLOGY_88(1)_9%2D20_;2010[59].pdf
Kar, Susanta and Ukil, Anindita and Sharma, Gunjan and Das, Pijush K (2010) MAPK-Directed Phosphatases Preferentially Regulate Pro- and Anti-Inflammatory Cytokines in Experimental Visceral leishmaniasis: involvement of distinct protein kinase C isoforms. Journal of Leukocyte Biology, 88. 09-20. |
|
| Relation |
http://dx.doi.org/10.1189/jlb.0909644
http://www.eprints.iicb.res.in/73/ |
|