| MAPK-directed phosphatases preferentially regulate pro- and anti-inflammatory cytokines in experimental visceral leishmaniasis: involvement of distinct protein kinase C isoforms. | |
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MedLine Citation:
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PMID: 20200403 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The role of phosphatases in the impairment of MAPK signaling, which is directly responsible for Leishmania-induced 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, PKCzeta was associated with induction of MKP3 and PP2A in infected macrophages, whereas PKCepsilon 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-alpha 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. |
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Authors:
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Susanta Kar; Anindita Ukil; Gunjan Sharma; Pijush K Das |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-03 |
Journal Detail:
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Title: Journal of leukocyte biology Volume: 88 ISSN: 1938-3673 ISO Abbreviation: J. Leukoc. Biol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-01 Completed Date: 2010-07-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8405628 Medline TA: J Leukoc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 9-20 Citation Subset: IM |
Affiliation:
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Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata, India. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Cystatins / pharmacology Cytokines / biosynthesis* Dual Specificity Phosphatase 1 / physiology* Dual Specificity Phosphatase 6 / physiology* Extracellular Signal-Regulated MAP Kinases / metabolism Female Isoenzymes / physiology* Leishmaniasis, Visceral / immunology* Mice Mice, Inbred BALB C Nitric Oxide Synthase Type II / genetics Protein Kinase C / physiology* Protein Phosphatase 2 / physiology* Th1 Cells / immunology Th2 Cells / immunology p38 Mitogen-Activated Protein Kinases / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cystatins; 0/Cytokines; 0/Isoenzymes; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.1.3.16/Protein Phosphatase 2; EC 3.1.3.48/Dual Specificity Phosphatase 1; EC 3.1.3.48/Dual Specificity Phosphatase 6; EC 3.1.3.48/Dusp1 protein, mouse; EC 3.1.3.48/Dusp6 protein, mouse |
| Comments/Corrections | |
Comment In:
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J Leukoc Biol. 2010 Jul;88(1):1-3
[PMID:
20591873
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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