The curative effect of fucoidan on visceral leishmaniasis is mediated by activation of MAP kinases through specific protein kinase C isoforms
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
The curative effect of fucoidan on visceral leishmaniasis is
mediated by activation of MAP kinases through specific
protein kinase C isoforms
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| Creator |
Sharma, Gunjan
Kar, Susanta Basu Ball, Writoban Ghosh, Kuntal Das, Pijush K |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Fucoidan can cure both antimony-sensitive and antimony-resistant visceral leishmaniasis through immune activation.
However, the signaling events underlying this cellular response remain uncharacterized. The present study reveals that fucoidan induces activation of p38 and ERK1/2 and NF-kB DNA binding in both normal and Leishmania donovani-infected macrophages, as revealed by western blotting and electrophoretic mobility shift assay (EMSA), respectively. Pharmacological inhibition of p38, ERK1/2 or the NF-kB pathway markedly attenuated fucoidan-induced pro-inflammatory cytokine synthesis and inducible nitric oxide synthase (iNOS) gene transcription, resulting in a
reduction of parasite clearance. To decipher the underlying mechanism of fucoidan-mediated parasite suppression, the
expression and functionality of various protein kinase C (PKC) isoforms were evaluated by immunoblotting and enzyme
activity assay. Fucoidan elicited an increase in expression and activity of PKC-a, -bI and -bII isoforms in infected
macrophages. Functional knockdown of PKC-a and -b resulted in downregulation of p38 and ERK1/2, along with a
marked reduction of IL-12 and TNF-a production in fucoidan-treated infected macrophages. Collectively, these results
suggest that the curative effect of fucoidan is mediated by PKC-dependent activation of the mitogen-activated protein
kinase (MAPK)/NF-kB pathway, which ultimately results in the production of nitric oxide (NO) and disease-resolving
pro-inflammatory cytokines.
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| Date |
2014
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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/2170/1/CELLULAR_%26_MOLECULAR_IMMUNOLOGY__V_11(_3_)263%2D274_;2014[112].pdf
Sharma, Gunjan and Kar, Susanta and Basu Ball, Writoban and Ghosh, Kuntal and Das, Pijush K (2014) The curative effect of fucoidan on visceral leishmaniasis is mediated by activation of MAP kinases through specific protein kinase C isoforms. Cellular & Molecular Immunology, 11 (3). pp. 263-274. |
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| Relation |
http://dx.doi.org/10.1038/cmi.2013.68
http://www.eprints.iicb.res.in/2170/ |
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