Leukotriene D4 induces gene expression in human monocytes through cysteinyl leukotriene type I receptor

Woszczek, Grzegorz; Chen, Liyuan; Nagineni, Sahrudaya; Kern, Steven J.; Barb, Jennifer; Munson, Peter J.; Logun, Carolea; Danner, Robert L.; Shelhamer, James H.

doi:10.1016/j.jaci.2007.09.013

Cited by 41 publications

(45 citation statements)

References 30 publications

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“…This correlates with the finding that cysteinyl LTs contribute to inflammatory reactions by induction of MCP-1 via the CCR2B receptor in THP-1 cells Woszczek et al, 2005;Hashimoto et al, 2009). This reported induction by MCP-1 was also observed in another monocytic leukemia cell line and was further supported by the enhanced activation of chemotactic activity observed in human monocytes (Woszczek et al, 2008a). Likewise, in THP-1 cells, montelukast and zafirlukast significantly down-regulated the chemotaxis induced by MCP-1 and p38 MAPK expression (Hung et al, 2006).…”

Section: Receptor Expression Patterns With Functional Significancesupporting

confidence: 58%

“…For example, in monocytes, LTD 4 induced p38 phosphorylation (Woszczek et al, 2008a), a pathway involved in the regulation of immediate-early gene expression. In a human epithelial cell line, CysLT 1 R activation has been shown to lead to either STAT-1 phosphorylation through PKC and ERK1/2 activation, causing enhanced intercellular cell adhesion molecule-1 expression and eosinophil adhesion (Profita et al, 2008), or to up-regulate mucin gene MUC2 transcription via a signaling pathway involving PKC and NF-B .…”

Section: Intracellular Signaling Pathways and Second-messenger Sysmentioning

confidence: 99%

See 1 more Smart Citation

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Bäck¹,

Dahlén²,

Drazen³

et al. 2011

Pharmacol Rev

130

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Section: Receptor Expression Patterns With Functional Significancesupporting

confidence: 58%

Section: Intracellular Signaling Pathways and Second-messenger Sysmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Bäck¹,

Dahlén²,

Drazen³

et al. 2011

Pharmacol Rev

130

View full text Add to dashboard Cite

“…Because U937 cells are a leukemia-derived cell line, we confi rmed our observation repeating some key experiments in primary HM that also have been reported to express mainly the CysLT 1 R transcript ( 44 ). We confi rmed that the LTD 4 -induced [Ca 2+ ] i transient was sensitive to montelukast and PTX (data not shown), indicating that this response is because of a CysLT 1 R activation ( 44 ) similar to the one observed in dU937 cells ( 16,29,30 ).…”

Section: Discussionsupporting

confidence: 83%

A role for inflammatory mediators in heterologous desensitization of CysLT1 receptor in human monocytes

Capra

Accomazzo

Gardoni

et al. 2010

Journal of Lipid Research

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Supplementary key wordsCysteinyl-leukotrienes (cysteinyl-LT) (i.e., LTC 4 , LTD 4 , and LTE 4 ) are members of a large family of biologically active lipid mediators rapidly generated at sites of infl ammation from arachidonic acid via the 5-lipoxygenase (5-LO) pathway ( 1 ). They are synthesized by infl ammatory cells, such as eosinophils, basophils, mast cells, and alveolar macrophages, in response to different immune and infl ammatory stimuli ( 2 ). Beyond their well-recognized role in asthma and immune disorders, cysteinyl-LTs are increasingly regarded as signifi cant infl ammatory factors in cancer, gastrointestinal, and cardiovascular diseases ( 3 ). In the past few years, the use of LT receptor antagonists as cardiovascular drugs has become a matter of considerable interest ( 4-6 ), as the presence of 5-LO, FLAP, and LT receptors transcripts has been shown in atherosclerotic lesions at various stages of development in human aorta, coronary arteries, and carotid arteries ( 3 ).The effects of cysteinyl-LTs are mediated through two offi cially recognized receptor subtypes: CysLT 1 and CysLT 2 ( 2, 3 ), which belong to the G-protein-coupled receptor (GPCR) gene superfamily and particularly to the purine receptor cluster (within the ␦ group) of the rhodopsin family ( 7 ). Over the years, several data in the literature suggested the existence of additional CysLT receptor (CysLT-R) subtypes in humans ( 3 ), and very recently new pharmacological targets have been identifi ed for cysteinylLTs, namely, two possible new receptor entities ( 8, 9 ) and a CysLT 1 /CysLT 2 heterodimer ( 10 ).

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“…Blockade of leukocyte chemotaxis has been reported to alleviate EAE (31,32). It has been reported that CysLTs induce chemotactic activity in eosinophils (33) and monocytes (34). We wondered whether CysLTs also induce the chemotaxis of pathogenic T cells in EAE.…”

Section: Montelukast Blocks Ltd 4 -Induced Leukocyte Chemotaxismentioning

confidence: 95%

Antiasthmatic Drugs Targeting the Cysteinyl Leukotriene Receptor 1 Alleviate Central Nervous System Inflammatory Cell Infiltration and Pathogenesis of Experimental Autoimmune Encephalomyelitis

Wang

et al. 2011

The Journal of Immunology

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Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and are considered to play a key role in inflammatory diseases such as asthma. Antagonists targeting the receptor of CysLTs (CysLT1) are currently used as antiasthmatic drugs. CysLTs have also been implicated in other inflammatory reactions. In this study, we report that in experimental autoimmune encephalomyelitis animals, CysLT1 is upregulated in immune tissue and the spinal cord, and CysLT levels in the blood and cerebrospinal fluid are also higher than in normal mice. Two clinically used antiasthma drugs, montelukast and zafirlukast, both targeting CysLT1, effectively block the CNS infiltration of inflammatory cells and thus reduce the incidence, peak severity, and cumulative clinical scores. Further study indicated that CysLT1 signaling does not affect the differentiation of pathogenic T helper cells. It might affect the pathogenesis of experimental autoimmune encephalomyelitis by increasing the secretion of IL-17 from myelin oligodendrocyte glycoprotein-specific T cells, increasing the permeability of the blood–brain barrier and inducing chemotaxis of T cells. These effects can be blocked by CysLT1 antagonists. Our findings indicate that the antiasthmatic drugs against CysLT1 can also be used to treat multiple sclerosis.

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Leukotriene D4 induces gene expression in human monocytes through cysteinyl leukotriene type I receptor

Abstract: Background-Cysteinyl leukotrienes (CysLTs) are important mediators of innate immune responsiveness and chronic inflammatory diseases. CysLTs acting through CysLT receptors can influence the migration and activity of cells, such as eosinophils, monocytes, and dendritic cells.

Cited by 41 publications

References 30 publications

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

A role for inflammatory mediators in heterologous desensitization of CysLT1 receptor in human monocytes

Antiasthmatic Drugs Targeting the Cysteinyl Leukotriene Receptor 1 Alleviate Central Nervous System Inflammatory Cell Infiltration and Pathogenesis of Experimental Autoimmune Encephalomyelitis

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