| Trp-P-1, a carcinogenic heterocyclic amine, inhibits lipopolysaccharide-induced maturation and activation of human dendritic cells. | |
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MedLine Citation:
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PMID: 21078543 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Carcinogens frequently provoke immunosuppressive effects thereby allowing cancer cells to persist in the host. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is a carcinogenic heterocyclic amine that is abundantly produced by overcooking meat and fish. Here, we investigated the effect of Trp-P-1 on dendritic cells (DCs), which play a central role in the appropriate activation of the host immune system. When human monocyte-derived DCs were stimulated with lipopolysaccharide (LPS), the DCs became mature with an increase in the expression of co-stimulatory receptors such as CD80, CD86, and MHC molecules and a decrease in phagocytic capacity. Trp-P-1 inhibited all of these phenomena under the same conditions. In addition, Trp-P-1 inhibited production of the cytokines TNF-α and IL-12 in LPS-stimulated DCs. Furthermore, DCs that were pre-exposed to Trp-P-1 were less efficient in inducing activation and proliferation of autologous T cells than control DCs. Trp-P-1 also attenuated the ability of DCs to directly kill T-cell lymphoma Jurkat cells. Mechanism studies showed that Trp-P-1 did not inhibit LPS-binding to Toll-like receptor 4 but interfered with the signaling pathways mediated through p38 kinase. In conclusion, our results suggest that Trp-P-1 is immunosuppressive by inhibiting the functionality of DCs that play an essential role in the appropriate induction of anti-cancer immune responses. |
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Authors:
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Jun Ho Jeon; Sun Kyung Kim; Jintaek Im; Ki Bum Ahn; Jung Eun Baik; Ok-Jin Park; Cheol-Heui Yun; Seung Hyun Han |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer letters Volume: 301 ISSN: 1872-7980 ISO Abbreviation: Cancer Lett. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-03 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 63-74 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Republic of Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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