Cysteinyl leukotrienes induce nuclear factor κb activation and rantes production in a murine model of asthma

Kawano, Tetsuya; Matsuse, Hiroto; Kondo, Yuki; Machida, Ikuko; Saeki, Sachiko; Tomari, Shinya; Mitsuta, Kazuko; Obase, Yasushi; Fukushima, Chizu; Shimoda, Terufumi; Kohno, Shigeru

doi:10.1067/mai.2003.1636

Cited by 68 publications

(65 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, both families of transcription factors (Egr and Fos) have been shown to be involved in the regulation of cell differentiation and inflammatory processes (28,29). cysLTs can activate the NF-B pathway in lung-derived mononuclear cells (30), and direct interactions between NF-B proteins and Egr and Fos proteins in the regulation of inflammatory gene expression have been demonstrated (31,32). It has also been shown that monocyte-derived DCs require for differentiation multidrug resistance protein 1 (ABCC1) transporter activity, which actively transports LTC 4 out of the cell (33).…”

Section: Discussionmentioning

confidence: 99%

IL-10 Inhibits Cysteinyl Leukotriene-Induced Activation of Human Monocytes and Monocyte-Derived Dendritic Cells

Woszczek

Chen

Nagineni

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

The immunoregulatory cytokine IL-10 plays an essential role in down-modulating adaptive and innate immune responses leading to chronic inflammatory diseases. In contrast, cysteinyl leukotrienes (cysLTs), important proinflammatory mediators of cell trafficking and innate immune responses, are thought to enhance immune reactions in the pathogenesis of diseases, such as bronchial asthma, atherosclerosis, and pulmonary fibrosis. The aim of this study was to determine the IL-10 regulatory role in cysLT-induced activation of human monocytes and monocyte-derived dendritic cells. Herein we show that cysLT-induced activation and chemotaxis of human monocytes and monocyte-derived immature dendritic cells (iDC) are inhibited by IL-10 pretreatment. IL-10 down-regulated cysLT type 1 and 2 receptors’ mRNA in a time- and concentration-dependent fashion. cysLT-induced activation of monocytes and iDCs measured by intracellular calcium flux and immediate-early gene expression (FBJ murine osteosarcoma viral oncogen homolog B and early growth response-2) was potently decreased by IL-10 and by the cysLT antagonist MK571. Chemotaxis of monocytes and iDCs to increasing concentrations of leukotriene D4 (LTD4) was also inhibited by IL-10. LTD4 enhanced iDC migration in response to CCL5. IL-10 selectively inhibited LTD4-induced chemotaxis without affecting migration to CCL5. These data indicate that cysLT-induced activation of human monocytes and dendritic cells may be specifically inhibited by IL-10, suggesting a direct link between the 5-lipoxygenase proinflammatory pathway and IL-10 regulatory mechanisms. Antileukotriene therapies may reproduce some regulatory mechanisms played by IL-10 in inflammatory processes.

show abstract

Section: Discussionmentioning

confidence: 99%

IL-10 Inhibits Cysteinyl Leukotriene-Induced Activation of Human Monocytes and Monocyte-Derived Dendritic Cells

Woszczek

Chen

Nagineni

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Hippocampal CysLT 1 R knockdown or blockade inhibited LPSinduced activation of the NF-κB pathway and production of proinflammatory cytokines CysLT 1 R has been reported to be implicated in neuroinflammation by regulating the NF-κB signaling pathway [23][24][25][26] , and LPS exposure activates NF-κB signaling by inducing the nuclear translocation of p65 [27] . To explore whether CysLT 1 R is involved in LPS-activated NF-κB signaling, the hippocampal level of NF-κB p65 in the nuclear fraction was detected by Western blot analysis.…”

Section: Hippocampal Cyslt 1 R Knockdown or Blockade Ameliorated Lpsimentioning

confidence: 99%

Hippocampal CysLT1R knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice

et al. 2017

View full text Add to dashboard Cite

Evidence suggests that neuroinflammation is involved in depression and that the cysteinyl leukotriene receptor 1 (CysLT 1 R) plays a potential pathophysiological role in several types of CNS disorders. Our previous study has shown that knockdown of hippocampal CysLT 1 R in mice prevents the depressive-like phenotype and neuroinflammation induced by chronic mild stress (CMS). Here, we examined the effects of hippocampal CysLT 1 R knockdown and CysLT 1 R blockade on LPS-induced depressive-like behavior in mice. We found that injection of LPS (0.5 mg/kg, ip) caused marked increase in hippocampal CysLT 1 R expression, which was reversed by pretreatment with fluoxetine (20 mg·kg -1 ·d -1 for 7 d, ig). Knockdown of hippocampal CysLT 1 R or blockade of CysLT 1 R by pretreatment with pranlukast (0.5 mg/kg, ip) significantly suppressed LPS-induced depressive behaviors, as evidenced by decreases in mouse immobility time in the forced swimming test (FST) and tail suspension test (TST) and latency to feed in the novelty-suppressed feeding (NSF) test. Moreover, both CysLT 1 R knockdown and CysLT 1 R blockade markedly prevented LPS-induced neuroinflammation, as shown by the suppressed activation of microglia and NF-κB signaling as well as the hippocampal levels of TNF-α and IL-1β in mice. Our results suggest that CysLT 1 R may be involved in LPS-induced depressive-like behaviors and neuroinflammation, and that downregulation of CysLT 1 R could be a novel and potential therapeutic strategy for the treatment of depression, at least partially due to its role in neuroinflammation.

show abstract

“…Leukotriene receptor agonists significantly reduce anaphylactic bronchoconstriction in passively sensitized human lung parenchyma in vitro compared with other anti-allergic drugs [18]. Leukotriene receptor agonists also have anti-inflammatory effects in a murine model of allergic asthma as they reduce airway eosinophilia and cytokine production from T lymphocytes [16]. Heterogeneous effects are characteristic of LTRAs.…”

Section: Pharmacologymentioning

confidence: 94%

“…The production of PAGE 9 cysLTs is increased in asthmatics, particularly during the early phase of bronchoconstriction that follows allergen challenge [14]. Cysteinyl LTs have far more powerful bronchoconstrictive effects than either methacholine or histamine, they induce AHR, vascular permeability and mucous production and exert proinflammatory effects including chemotactic activity for eosinophils and cytokine production from lymphocytes [15,16]. All of these actions are closely associated with the pathogenesis of asthma.…”

Section: Action Of Cyslts In Asthmamentioning

confidence: 99%

Leukotriene receptor antagonists pranlukast and montelukast for treating asthma

Matsuse

Kohno

2013

Expert Opinion on Pharmacotherapy

Self Cite

View full text Add to dashboard Cite

IntroductionThe prevalence of bronchial asthma, which is a chronic inflammatory disorder of the airway, is increasing worldwide. Although inhaled corticosteroids (ICS) play a central role in the treatment of asthma, they cannot achieve good control for all asthmatics and medications such as leukotriene receptor antagonists (LTRAs) with bronchodilatory and anti-inflammatory effects often serve as alternatives or add-on drugs. Several issues such as predicted responses, effects of peripheral airway and airway remodeling and alternative administration routes remain to be clarified before LTRAs PAGE 3 could serve a more effective role in the treatment of asthma. Areas covered

show abstract

Cysteinyl leukotrienes induce nuclear factor κb activation and rantes production in a murine model of asthma

Cited by 68 publications

References 37 publications

IL-10 Inhibits Cysteinyl Leukotriene-Induced Activation of Human Monocytes and Monocyte-Derived Dendritic Cells

IL-10 Inhibits Cysteinyl Leukotriene-Induced Activation of Human Monocytes and Monocyte-Derived Dendritic Cells

Hippocampal CysLT1R knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice

Leukotriene receptor antagonists pranlukast and montelukast for treating asthma

Contact Info

Product

Resources

About