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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2001-7-25
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pubmed:abstractText |
Prior to the activation of CD4 (+) T cells, exogenous proteins must be digested by endo/lysosomal enzymes in antigen-presenting cells (APC) to produce antigenic peptides that are able to be presented on class II molecules of the MHC. Studies described here inspect the functional significance of cathepsin L inhibition for antigen processing and T (h) 1/T (h) 2 differentiation in experimental leishmaniasis. We first demonstrated using in vitro systems that cathepsin L is one of the candidate endo/lysosomal enzymes in processing of soluble Leishmania antigen (SLA) and that its specific inhibitor, CLIK148, modulated the processing of SLA. BALB/c mice are known to be susceptible to infection with Leishmania major. Interestingly, treatment of BALB/c mice with CLIK148 exacerbated the infection by enhancing the development of SLA-specific T (h) 2-type response such as production of IL-4 and generation of T (h) 2-dependent specific IgE/IgG1 antibodies. Moreover, addition of CLIK148 in incubation of a SLA-specific CD4 (+) T cell line with APC up-regulated the production of IL-4. However, CLIK148 did not exert any direct influence on the function of T cells themselves. Taken together, these findings suggest that treatment of host mice with CLIK148 affects the processing of SLA in APC, resulting in the potentiation of T (h) 2-type immune responses and thus leading to exacerbation of the infection. Furthermore, endo/lysosomal cathepsin L was found to be functionally distinct from previously described cathepsins B and D.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Protozoan,
http://linkedlifedata.com/resource/pubmed/chemical/CA 074 methyl ester,
http://linkedlifedata.com/resource/pubmed/chemical/CLIK 148,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin L,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins,
http://linkedlifedata.com/resource/pubmed/chemical/Ctsl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Dipeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Epoxy Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0953-8178
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
975-82
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11470767-Adjuvants, Immunologic,
pubmed-meshheading:11470767-Animals,
pubmed-meshheading:11470767-Antigen Presentation,
pubmed-meshheading:11470767-Antigens, Protozoan,
pubmed-meshheading:11470767-Cathepsin L,
pubmed-meshheading:11470767-Cathepsins,
pubmed-meshheading:11470767-Cell Differentiation,
pubmed-meshheading:11470767-Cell Line,
pubmed-meshheading:11470767-Cysteine Endopeptidases,
pubmed-meshheading:11470767-Cysteine Proteinase Inhibitors,
pubmed-meshheading:11470767-Dipeptides,
pubmed-meshheading:11470767-Endosomes,
pubmed-meshheading:11470767-Epoxy Compounds,
pubmed-meshheading:11470767-Female,
pubmed-meshheading:11470767-Injections, Intraperitoneal,
pubmed-meshheading:11470767-Leishmania major,
pubmed-meshheading:11470767-Leishmaniasis, Cutaneous,
pubmed-meshheading:11470767-Lysosomes,
pubmed-meshheading:11470767-Mice,
pubmed-meshheading:11470767-Mice, Inbred BALB C,
pubmed-meshheading:11470767-Pyridines,
pubmed-meshheading:11470767-Solubility,
pubmed-meshheading:11470767-Th2 Cells
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pubmed:year |
2001
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pubmed:articleTitle |
Treatment with cathepsin L inhibitor potentiates Th2-type immune response in Leishmania major-infected BALB/c mice.
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pubmed:affiliation |
Department of Parasitology and Immunology, The University of Tokushima School of Medicine, 3 Kuramoto-cho, Tokushima 770-8503, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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