Immunomodulatory Peptide from Cystatin, a Natural Cysteine Protease Inhibitor, against Leishmaniasis as a Model Macrophage Disease▿
Identifieur interne : 000E83 ( Main/Exploration ); précédent : 000E82; suivant : 000E84Immunomodulatory Peptide from Cystatin, a Natural Cysteine Protease Inhibitor, against Leishmaniasis as a Model Macrophage Disease▿
Auteurs : Snigdha Mukherjee [Inde] ; Anindita Ukil [Inde] ; Pijush K. Das [Inde]Source :
- Antimicrobial Agents and Chemotherapy [ 0066-4804 ] ; 2007.
Abstract
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 μg/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.
Url:
DOI: 10.1128/AAC.01555-06
PubMed: 17339373
PubMed Central: 1855531
Affiliations:
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Das</name><affiliation wicri:level="1"><nlm:aff id="aff0">Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology, Calcutta, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology, Calcutta</wicri:regionArea><wicri:noRegion>Calcutta</wicri:noRegion></affiliation></author></analytic><series><title level="j">Antimicrobial Agents and Chemotherapy</title><idno type="ISSN">0066-4804</idno><idno type="eISSN">1098-6596</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Cystatin, a natural cysteine protease inhibitor, has strong antileishmanial activity, which is due to its potential to induce nitric oxide (NO) generation from macrophages. 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