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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 \u03bcg\/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.<\/jats:p>","DOI":"10.1128\/aac.01555-06","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T01:42:38Z","timestamp":1173145358000},"page":"1700-1707","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Immunomodulatory Peptide from Cystatin, a Natural Cysteine Protease Inhibitor, against Leishmaniasis as a Model Macrophage Disease"],"prefix":"10.1128","volume":"51","author":[{"given":"Snigdha","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology, Calcutta, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anindita","family":"Ukil","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology, Calcutta, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pijush K.","family":"Das","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology, Calcutta, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)67380-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03768.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.2.941-943.1990"},{"key":"e_1_3_2_5_2","first-page":"1371","volume":"379","year":"1998","unstructured":"Blankenvoore, M. 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