Nicotine stereoisomers and cotinine stimulate prostaglandin E2 but inhibit thromboxane B2 and leukotriene E4 synthesis in whole blood

Saareks, Virpi; Muchá, I.; Sievi, Eeva; Vapaatalo, Heikki; Riutta, Asko

doi:10.1016/s0014-2999(98)00384-7

Cited by 31 publications

(25 citation statements)

References 47 publications

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“…The current study identifies nicotine as the likely primary constituent in cigarette smoke involved in cigarette smoke-induced COX-2 and PGE 2 production by maturing DCs. Our findings are consistent with the work of others showing induction of COX-2 and secreted PGE 2 by nicotinic stimulation of microglia (De Simone et al, 2005), fibroblasts (Ho and Chang, 2006), monocytes (Payne et al, 1996), and whole blood (Saareks et al, 1998). The biologic effects of nicotine on DCs are mediated through the alpha7-nicotinic acetylcholine receptor, which is expressed on both immature and mature DCs (data not shown) and has been shown to negatively regulate synthesis and release of tumor necrosis factor (TNF)-alpha in macrophages.…”

Section: Discussionsupporting

confidence: 94%

Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Vassallo

Kroening

Parambil

et al. 2008

Molecular Immunology

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Chronic airway inflammation is a cardinal feature of chronic obstructive pulmonary disease (COPD), a destructive cigarette smoke-induced lung disease. Although it is apparent that dendritic cells (DCs) are an important constituent of the chronic inflammatory cell influx found in airways of COPD patients, the functional roles of DCs in the pathogenesis of smoking-induced emphysema are unknown. We postulated that DCs activated by cigarette smoke constituents directly participate in the chronic inflammation that characterizes COPD airways. Concordant with this hypothesis, we observed that incubation of DCs with cigarette smoke extract (CSE), and chronic exposure of mice to cigarette smoke, both augmented the generation of neutrophilic chemokines by immature and lipopolysaccharide (LPS) or CD40L-matured DCs. The generation of interleukin-8 (CXCL8/IL-8) by human DCs conditioned with CSE was suppressed by the antioxidant n-acetyl cysteine (NAC), implying the involvement of oxidant sensitive pathways as a primary mechanism involved in the enhanced CXCL8/IL-8 generation. Cigarette smoke extract and nicotine also augment the production of secreted prostaglandin E 2 and intracellular cyclooxygenase-2 (COX-2) in maturing DCs. Whereas NAC suppressed production of CXCL8 by CSEconditioned DCs, it augmented production of PGE 2 and cellular COX-2 levels in maturing DCs. These studies indicate that the stimulation of DCs by cigarette smoke-induced oxidative stress and nicotine promote the generation of pro-inflammatory responses that promote chronic inflammation in smokers. Certain pharmacologic strategies such as anti-oxidant therapy may be only partially effective in mitigating cigarette smoke-induced pro-inflammatory DC-mediated responses in smokers.

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Section: Discussionsupporting

confidence: 94%

Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Vassallo

Kroening

Parambil

et al. 2008

Molecular Immunology

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“…There is increasing evidence that exposure to carcinogens such as ultraviolet B light (Athar et al, 2001), the tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (El-Bayoumy et al, 1999) and nicotine (Saareks et al, 1998), and helicobacter pylori (Konturek et al, 2000;Sawaoka et al, 1998a) leads to the upregulation of COX-2 in the affected tissue Carcinogens act, at least in part, through the induction of growth factors and activation of growth factor receptors. An example of a growth factor known to be induced by carcinogenic insults is the epidermal growth factor receptor (EGFR) which is upregulated in many malignant and pre-malignant conditions including those of the lung (Cox et al, 2000).…”

Section: The Immune Response and Angiogenesis In Malignant Diseasementioning

confidence: 99%

Chronic immune activation and inflammation as the cause of malignancy

2001

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Summary Several chronic infections known to be associated with malignancy have established oncogenic properties. However the existence of chronic inflammatory conditions that do not have an established infective cause and are associated with the development of tumours strongly suggests that the inflammatory process itself provides the prerequisite environment for the development of malignancy. This environment includes upregulation of mediators of the inflammatory response such as cyclo-oxygenase (COX)-2 leading to the production of inflammatory cytokines and prostaglandins which themselves may suppress cell mediated immune responses and promote angiogenesis. These factors may also impact on cell growth and survival signalling pathways resulting in induction of cell proliferation and inhibition of apoptosis. Furthermore, chronic inflammation may lead to the production of reactive oxygen species and metabolites such as malondialdehyde within the affected cells that may in turn induce DNA damage and mutations and, as a result, be carcinogenic. Here it is proposed that the conditions provided by a chronic inflammatory environment are so essential for the progression of the neoplastic process that therapeutic intervention aimed at inhibiting inflammation, reducing angiogenesis and stimulating cell mediated immune responses may have a major role in reducing the incidence of common cancers. 473-483 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2001.1943, available online at http://www.idealibrary.com on http://www.bjcancer.com (Kirk and Clements, 1999;Lewis et al, 1999). Furthermore, in the majority of colorectal tumours not associated with inflammatory bowel disease, histology shows that the precursor lesions, whether adenomas or polyps, are often inflammatory in nature (Higaki et al, 1999). THE INFLAMMATORY ENVIRONMENT ASSOCIATED WITH THE SUBSEQUENT DEVELOPMENT OF CANCERWhereas the association between chronic immune activation and the development of cancer has been recognized for some years, only recently have we begun to understand the mechanisms underlying this phenomenon. The first concerns the nature of the local and systemic immune response seen in patients with chronic inflammatory conditions known to be associated with the development of malignant disease. Immune responses may be broadly divided into two categories -cell mediated immunity and humoral immunity. Cell mediated immunity (CMI) is associated with CD4 + T-lymphocytes which characteristically produce the cytokines interleukin(IL)-2, interferon-γ and tumour necrosis factor(TNF)-α (Thl-lymphocytes). Humoral immunity (HI) is associated with CD4+ T-lymphocytes which characteristically produce IL-4, IL-6 and IL-10 (Th2) (Mosmann and Coffman, 1989).Recent experimental evidence suggests that exposure to a foreign antigen results in upregulation of the non-specific pro-inflammatory cytokines IL-1α and -β and the Th1 cytokines in inflammatory cells. Cyclooxygenase (COX)-1 and COX-2 are among the most important enzymes involved in the regulation of th...

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“…Recently, we found that PGE 2 inhibited IL-18 production in human monocytes treated with LPS via prostanoid EP 2 -and EP 4 -receptors (10). Nicotine is reported to induce the expression of COX-2 and the synthesis of one of its major products, PGE 2 , in macrophages through α7-nAChR stimulation (11). However little is known about the effect of nicotine on the production of IL-18 and -12.…”

mentioning

confidence: 99%

α7 Nicotinic Acetylcholine Receptor Stimulation Inhibits Lipopolysaccharide-Induced Interleukin-18 and -12 Production in Monocytes

et al. 2006

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Abstract. Nicotine inhibited interleukin (IL)-18 and -12 production in lipopolysaccharide (LPS)-stimulated monocytes, and the action of nicotine was antagonized by a non-selective and a selective α7 nicotinic acetylcholine receptor (α7-nAChR) antagonist, suggesting that the stimulation of α7-nAChR may be involved in the action of nicotine. Nicotine is reported to induce prostaglandin E 2 (PGE 2 ) production in monocytes through the up-regulation of cyclooxygenase (COX)-2 expression. PGE 2 is known to increase cAMP levels and to activate protein kinase A (PKA). COX-2 and PKA inhibitors prevented the action of nicotine, indicating that the mechanism of action of nicotine may be via endogenous PGE 2 production.

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Nicotine stereoisomers and cotinine stimulate prostaglandin E2 but inhibit thromboxane B2 and leukotriene E4 synthesis in whole blood

Cited by 31 publications

References 47 publications

Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Chronic immune activation and inflammation as the cause of malignancy

α7 Nicotinic Acetylcholine Receptor Stimulation Inhibits Lipopolysaccharide-Induced Interleukin-18 and -12 Production in Monocytes

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