Acrolein in cigarette smoke inhibits T-cell responses

Lambert, Cherie; McCue, Jesica M.; Portas, Mary; Ouyang, Yanli; Li, Jimei; Rosano, Thomas G.; Lazis, Alexander; Freed, Brian M.

doi:10.1016/j.jaci.2005.05.046

Cited by 114 publications

(93 citation statements)

References 35 publications

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“…Recently, Lambert et al [102] reported on the immune-suppressing effects of cigarette smoke. Using human T-cells, they determined the effects of acrolein and related aldehydes on the production of proinflammatory cytokines, including interleukin-2 (IL-2), IL-10, granulocytemacrophage colony-stimulating factor, interferon-γ, and tumor necrosis factor α (TNF-α).…”

Section: Acrolein As a Modulator Of Stress-mediated Gene Activationmentioning

confidence: 99%

“…Acrolein inhibited the production of proinflammatory cytokines with an IC 50 of 3 μM, which could be physiologically relevant in view of the amounts of acrolein generated by a single cigarette (60 μg = 1.1 μmol). The saturated aldehydes, acetaldehyde, propanal, and butanal, were inactive, presumably due to their inability to form Michael-type adducts with cysteine residues in NF-κB [102]. NF-κB-DNA binding was decreased by acrolein after mitogenic stimulation of T cells.…”

Section: Acrolein As a Modulator Of Stress-mediated Gene Activationmentioning

confidence: 99%

“…Using MS/MS, Lambert et al [102] identified acrolein-modified amino acid residues in the p50 subunit, the DNA-binding domain of NFκB, after exposure of the protein to acrolein, i. e., Cys-61, Cys-87, Cys-118, Cys-123, Cys-261, Cys-272, Arg-230, and His-306. The in vitro experiment also revealed acrolein adduction to Arg-307, forming six-membered heterocycle.…”

Section: Acrolein As a Modulator Of Stress-mediated Gene Activationmentioning

confidence: 99%

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Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease

Stevens

Maier

2008

Molecular Nutrition Food Res

599

634

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Acrolein (2-propenal) is ubiquitously present in (cooked) foods and in the environment. It is formed from carbohydrates, vegetable oils and animal fats, amino acids during heating of foods, and by combustion of petroleum fuels and biodiesel. Chemical reactions responsible for release of acrolein include heat-induced dehydration of glycerol, retro-aldol cleavage of dehydrated carbohydrates, lipid peroxidation of polyunsaturated fatty acids, and Strecker degradation of methionine and threonine. Smoking of tobacco products equals or exceeds the total human exposure to acrolein from all other sources. The main endogenous sources of acrolein are myeloperoxidase-mediated degradation of threonine and amine oxidase-mediated degradation of spermine and spermidine, which may constitute a significant source of acrolein in situations of oxidative stress and inflammation. Acrolein is metabolized by conjugation with glutathione and excreted in the urine as mercapturic acid metabolites. Acrolein forms Michael adducts with ascorbic acid in vitro, but the biological relevance of this reaction is not clear. The biological effects of acrolein are a consequence of its reactivity towards biological nucleophiles such as guanine in DNA and cysteine, lysine, histidine, and arginine residues in critical regions of nuclear factors, proteases, and other proteins. Acrolein adduction disrupts the function of these biomacromolecules which may result in mutations, altered gene transcription, and modulation of apoptosis.

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Section: Acrolein As a Modulator Of Stress-mediated Gene Activationmentioning

confidence: 99%

Section: Acrolein As a Modulator Of Stress-mediated Gene Activationmentioning

confidence: 99%

Section: Acrolein As a Modulator Of Stress-mediated Gene Activationmentioning

confidence: 99%

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Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease

Stevens

Maier

2008

Molecular Nutrition Food Res

599

634

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“…The dihydroxyphenols (hydroquinone and catechol) in the particulate phase inhibit T cell proliferation by blocking cell cycle progression in late G 1 and S phase (8 -12). In addition, the ␣,␤-unsaturated aldehydes, acrolein (CH 2 ACHCHO) and crotonaldehyde (CH 3 CHACHCHO) in the gas phase of cigarette smoke inhibit the production of several proinflammatory cytokines including IL-2, 4 tumor necrosis factor-␣, and granulocyte-macrophage colony-stimulating factor, with an IC 50 of 3 and 6 M, respectively (13). The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) have IC 50 values of Ͼ1500 M. The typical cigarette generates sufficient acrolein to produce more than a liter of a 3 M solution (13).…”

mentioning

confidence: 99%

Acrolein Inhibits Cytokine Gene Expression by Alkylating Cysteine and Arginine Residues in the NF-κB1 DNA Binding Domain

Lambert¹,

Li²,

Jonscher

et al. 2007

Journal of Biological Chemistry

Self Cite

105

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Cigarette smoke is a potent inhibitor of pulmonary T cell responses, resulting in decreased immune surveillance and an increased incidence of respiratory tract infections. The ␣,␤-unsaturated aldehydes in cigarette smoke (acrolein and crotonaldehyde) inhibited production of interleukin-2 (IL-2), IL-10, granulocyte-macrophage colony-stimulating factor, interferon-␥, and tumor necrosis factor-␣ by human T cells but did not inhibit production of IL-8. The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) in cigarette smoke were inactive. Acrolein inhibited induction of NF-B DNA binding activity after mitogenic stimulation of T cells but had no effect on induction of NFAT or AP-1. Acrolein inhibited NF-B1 (p50) binding to the IL-2 promoter in a chromatin immunoprecipitation assay by >99%. Using purified recombinant p50 in an electrophoretic mobility shift assay, we demonstrated that acrolein was 2000-fold more potent than crotonaldehyde in blocking DNA binding to an NF-B consensus sequence. Matrix-assisted laser desorption/ionization time-offlight and tandem mass spectrometry demonstrated that acrolein alkylated two amino acids (Cys-61 and Arg-307) in the DNA binding domain. Crotonaldehyde reacted with Cys-61, but not Arg-307, whereas the saturated aldehydes in cigarette smoke did not react with p50. These experiments demonstrate that aldehydes in cigarette smoke can regulate gene expression by direct modification of a transcription factor.Cigarette smoke produces profound suppression of pulmonary immunity, resulting in an increased incidence and severity of respiratory tract infections. A recent Institute of Medicine study concluded that smoking increased the incidence of influenza and bacterial pneumonia and accounted for 19,000 smoking-related deaths per year (1). Children infected with Mycobacterium tuberculosis are five times more likely to develop pulmonary tuberculosis if exposed to cigarette smoke (2), and smoking doubles the risk of developing Pneumocystis carinii pneumonia in human immunodeficiency virus-infected individuals (3). Several studies have demonstrated that smoking suppresses T and B cell responses in the lungs without affecting cells in the peripheral blood (4 -7), but little research has been done to elucidate the underlying mechanism behind this phenomenon.We have recently identified two classes of immunosuppressive compounds in cigarette smoke. The dihydroxyphenols (hydroquinone and catechol) in the particulate phase inhibit T cell proliferation by blocking cell cycle progression in late G 1 and S phase (8 -12). In addition, the ␣,␤-unsaturated aldehydes, acrolein (CH 2 ACHCHO) and crotonaldehyde (CH 3 CHACHCHO) in the gas phase of cigarette smoke inhibit the production of several proinflammatory cytokines including IL-2, 4 tumor necrosis factor-␣, and granulocyte-macrophage colony-stimulating factor, with an IC 50 of 3 and 6 M, respectively (13). The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) have IC 50 values of Ͼ1500 M. The typical cigarett...

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“…Humans are exposed to acrolein via cigarette smoke, wood, plastic, overheated cooking fats and drinking water [12][13][14]. In addition to exogenous sources of exposure, acrolein is produced in situ during the normal catabolism of various amino acid and also is a toxic metabolite of cyclophosphamide, an anti-cancer drug [13].…”

Section: Introductionmentioning

confidence: 99%

Acrolein sensitizes human renal cancer Caki cells to TRAIL-induced apoptosis via ROS-mediated up-regulation of death receptor-5 (DR5) and down-regulation of Bcl-2

Yang

Woo

Choi

et al. 2011

Experimental Cell Research

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Acrolein in cigarette smoke inhibits T-cell responses

Cited by 114 publications

References 35 publications

Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease

Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease

Acrolein Inhibits Cytokine Gene Expression by Alkylating Cysteine and Arginine Residues in the NF-κB1 DNA Binding Domain

Acrolein sensitizes human renal cancer Caki cells to TRAIL-induced apoptosis via ROS-mediated up-regulation of death receptor-5 (DR5) and down-regulation of Bcl-2

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