Leishmania donovani Suppresses Activated Protein 1 and NF-�B Activation in Host Macrophages via Ceramide Generation: Involvement of Extracellular Signal-Regulated Kinase
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Leishmania donovani Suppresses Activated Protein 1 and NF-�B
Activation in Host Macrophages via Ceramide Generation:
Involvement of Extracellular Signal-Regulated Kinase
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| Creator |
Ghosh, Sanjukta
Bhattacharyya, Sandip Sirkar, Madhumita Sa, Gouri Shankar Das, Tanya Majumdar, Debashis Roy, Syamal Majumdar, Subrata |
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| Subject |
Infectious Diseases and Immunology
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| Description |
In vitro infection of murine peritoneal macrophages with the protozoan Leishmania donovani has been found
to alter the signaling parameters of the host. The present study indicates that the enhancement of intracellular
ceramide level in macrophages after infection is a major event relating to macrophage dysfunction. We have
previously demonstrated that increased ceramide synthesis in host macrophages was involved in the dephosphorylation
of extracellular signal-regulated kinase (ERK). In the present study, we further show that downregulation
of ERK by ceramide was found to be associated with the inhibition of activated protein 1 (AP-1) and
NF-�B transactivation. Pharmacological inhibition of ceramide synthesis by Fumonisin B1 restored the
induction of AP-1 and NF-�B DNA-binding activities in infected BALB/c macrophages. On the contrary, in the
case of macrophages from the leishmaniasis-resistant C.D2 mice, L. donovani failed to induce sustained
ceramide synthesis. Enhanced mitogen-activated protein kinase phosphorylation, AP-1 and NF-�B DNAbinding
activity, and the generation of nitric oxide (NO) were observed in L. donovani-infected C.D2 macrophages.
ERK activation was necessary for the activation of transcription factors AP-1 and NF-�B, NO
generation, and restriction of the parasite burden in the resistant murine host macrophages. Hence, the
induction of ceramide synthesis in host macrophages appears to be instrumental and one of the turning points
leading to silencing of the macrophage antileishmanial responses
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| Publisher |
American Society for Microbiology
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| Date |
2002
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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/542/1/INFECTION_AND_IMMUNITY_70(12)6828%2D6838_;2002[7].pdf
Ghosh, Sanjukta and Bhattacharyya, Sandip and Sirkar, Madhumita and Sa, Gouri Shankar and Das, Tanya and Majumdar, Debashis and Roy, Syamal and Majumdar, Subrata (2002) Leishmania donovani Suppresses Activated Protein 1 and NF-�B Activation in Host Macrophages via Ceramide Generation: Involvement of Extracellular Signal-Regulated Kinase. Infection and Immunity, 70 (12). pp. 6828-6838. |
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| Relation |
http://dx.doi.org/10.1128/IAI.70.12.6828–6838.2002
http://www.eprints.iicb.res.in/542/ |
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