Immunomodulatory Peptide from Cystatin, a Natural Cysteine Protease Inhibitor, against Leishmaniasis as a Model Macrophage Disease
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Immunomodulatory Peptide from Cystatin, a Natural Cysteine
Protease Inhibitor, against Leishmaniasis as a Model
Macrophage Disease
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| Creator |
Mukherjee, Snigdha
Ukil, Anindita Das, Pijush K |
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| Subject |
Cell Biology & Physiology
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| Description |
Cystatin, a natural cysteine protease inhibitor, has strong antileishmanial activity, which is due to its
potential to induce nitric oxide (NO) generation from macrophages. Cysteine protease-inhibitory activity and
NO-up-regulatory activity correspond to different regions, as revealed by the dissection of cystatin cDNA into
nonoverlapping fragments. By using synthetic overlapping peptides, the NO-up-regulatory activity was found
to be confined to a 10-mer sequence. In addition to having reasonable inhibitory effects on amastigote
multiplication within macrophages (50% inhibitory concentration, 5.2 �g/ml), 97 and 93% suppression,
respectively, of liver and spleen parasite burdens was achieved with the 10-mer peptide at a dose of 0.5 mg/kg
of body weight/day, given consecutively for 4 days along with a suboptimal dose of gamma interferon in a 45-day
mouse model of visceral leishmaniasis. Peptide treatment modulated the levels of cytokine secretion by infected
splenocytes, with increased levels of interleukin-12 and tumor necrosis factor alpha and increased inducible
NO synthase production, and also resulted in resistance to reinfection. The generation of a natural peptide
from cystatin with robust immunomodulatory potential may therefore provide a promising therapeutic agent
for macrophage-associated diseases.
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| Date |
2007
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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/316/1/ANTIMICROBIAL_AGENTS_AND_CHEMOTHERAPY%2C_51(_5)%2C_1700%2D1707_[89].pdf
Mukherjee, Snigdha and Ukil, Anindita and Das, Pijush K (2007) Immunomodulatory Peptide from Cystatin, a Natural Cysteine Protease Inhibitor, against Leishmaniasis as a Model Macrophage Disease. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 51 (5). pp. 1700-1707. |
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| Relation |
http://dx.doi.org/10.1128/AAC.01555-06
http://www.eprints.iicb.res.in/316/ |
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