Document Detail


Trp-P-1, a carcinogenic heterocyclic amine, inhibits lipopolysaccharide-induced maturation and activation of human dendritic cells.
MedLine Citation:
PMID:  21078543     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer letters     Volume:  301     ISSN:  1872-7980     ISO Abbreviation:  Cancer Lett.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  63-74     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
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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