PMID- 15762874
OWN - NLM
STAT- MEDLINE
DCOM- 20050516
LR  - 20181113
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 140
IP  - 1
DP  - 2005 Apr
TI  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone, a component of tobacco smoke, 
      modulates mediator release from human bronchial and alveolar epithelial cells.
PG  - 46-53
AB  - Respiratory epithelial cells are known to contribute to immune responses through 
      the release of mediators. The aim of this study was to characterize the 
      immunomodulatory effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 
      a tobacco carcinogen, on respiratory epithelial cells and to compare two 
      metabolic pathways, alpha-methylhydroxylation and alpha-methylenehydroxylation, 
      involved in these effects using selective precursors, 
      4-(acetoxy-methylnitrosamino)-1-(3-pyridil)-1-butanone (NNKOAc) and N-nitroso 
      (acetoxymethyl) methylamine (NDMAOAc), respectively. Human bronchial and alveolar 
      epithelial cell lines, BEAS-2B and A549, respectively, were treated with NNK, 
      NNKOAc and NDMAOAc for 24 h with and without tumour necrosis factor (TNF) and 
      mediators released in cell-free supernatants were measured by enzyme-linked 
      immunosorbent assay (ELISA). NNK significantly inhibited interleukin (IL)-8, IL-6 
      and monocyte chemoattractant protein-1 (MCP-1) production in both cell types. 
      Similar results were observed with primary bronchial and alveolar epithelial 
      cells. Although NNK increased prostaglandin E(2) (PGE(2)) production by A549 
      cells, its immunomodulatory effects were not mediated by PGE(2) according to the 
      results with cyclo-oxygenase inhibitors. NNKOAc mimicked NNK effects, whereas 
      NDMAOAc significantly inhibited IL-8 production in BEAS-2B cells and MCP-1 in 
      both cell types. These results demonstrate that NNK and its reactive metabolites 
      have immunosuppressive effects on respiratory epithelial cells, which could 
      contribute to the increased respiratory infections observed in smokers and the 
      development and/or the progression of lung cancer.
FAU - Proulx, L I
AU  - Proulx LI
AD  - Centre de Recherche, Hopital Laval, Institut Universitaire de Cardiologie et de 
      Pneumologie de l'Universite Laval, Sainte-Foy, Quebec, Canada.
FAU - Gaudreault, M
AU  - Gaudreault M
FAU - Turmel, V
AU  - Turmel V
FAU - Augusto, L A
AU  - Augusto LA
FAU - Castonguay, A
AU  - Castonguay A
FAU - Bissonnette, E Y
AU  - Bissonnette EY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (CCL2 protein, human)
RN  - 0 (Carcinogens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Nitrosamines)
RN  - 0 (Pyridines)
RN  - 127686-49-1 (4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone)
RN  - 56856-83-8 (methyl(acetoxymethyl)nitrosamine)
RN  - 7S395EDO61 (4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - M43H21IO8R (Dimethylnitrosamine)
SB  - IM
MH  - Bronchi/*immunology
MH  - Carcinogens/*pharmacology
MH  - Cell Line
MH  - Chemokine CCL2/immunology
MH  - Cytokines/*immunology
MH  - Dimethylnitrosamine/*analogs & derivatives/immunology/pharmacology
MH  - Dinoprostone/biosynthesis/immunology
MH  - Epithelial Cells/immunology
MH  - Humans
MH  - Hydroxylation
MH  - Interleukin-6/immunology
MH  - Interleukin-8/immunology
MH  - Nitrosamines/*immunology/pharmacology
MH  - Pulmonary Alveoli/*immunology
MH  - Pyridines/immunology/pharmacology
PMC - PMC1809332
EDAT- 2005/03/15 09:00
MHDA- 2005/05/17 09:00
PMCR- 2006/04/01
CRDT- 2005/03/15 09:00
PHST- 2005/03/15 09:00 [pubmed]
PHST- 2005/05/17 09:00 [medline]
PHST- 2005/03/15 09:00 [entrez]
PHST- 2006/04/01 00:00 [pmc-release]
AID - CEI2739 [pii]
AID - 10.1111/j.1365-2249.2005.02739.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2005 Apr;140(1):46-53. doi: 10.1111/j.1365-2249.2005.02739.x.