Effects of a leukotriene B4 receptor antagonist on bleomycin-induced pulmonary fibrosis

Izumo, Takehiro; Kondo, Mitsuko; Nagai, Atsushi

doi:10.1183/09031936.00143708

Cited by 48 publications

(27 citation statements)

References 28 publications

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“…LTB 4 is a well-known chemoattractant for neutrophils and for other inflammatory cells, yet there are few studies investigating its profibrotic effect. A previous in vitro study showed that it is also a chemoattractant for fibroblasts [5], and a recent study showed that treatment with an LTB 4 receptor antagonist for 3 weeks inhibited the development of bleomycin-induced pulmonary fibrosis in mice [28]. These studies suggest that LTB 4 is involved in the pathogenesis of pulmonary fibrosis.…”

Section: Discussionmentioning

confidence: 65%

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

Shimbori

Shiota²,

Okunishi³

2012

Int Arch Allergy Immunol

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Background: Although cysteinyl leukotrienes (CysLTs) have been implicated in the etiology of acute inflammatory diseases, recent studies have suggested that they also directly stimulate fibroblasts. However, their precise role in the pathogenesis of pulmonary fibrosis is unclear. Methods: In this study, we evaluated the effect of both short- and long-term treatment with pranlukast, a CysLT type 1 (CysLT₁) receptor antagonist, on silica-induced pulmonary fibrosis in mice, which is characterized by persistent progression of fibrosis in the chronic phase. Pranlukast (30 mg/kg/day) was administered orally to mice for 2 or 10 weeks after intratracheal silica instillation. Results: Pranlukast treatment for 10 weeks significantly attenuated the progression of pulmonary fibrosis, and decreased the content of CysLTs and LTB₄, which were markedly increased in the bronchoalveolar lavage fluid (BALF) and lung tissues of silica-instilled mice in the chronic phase. However, pranlukast treatment for 2 weeks neither affected the acute inflammatory response induced by silica instillation nor inhibited the onset of fibrosis. The expression of TGF-β1 and TNF-α was not affected by pranlukast treatment for either 2 or 10 weeks. Conclusions: Pranlukast attenuates the progression of pulmonary fibrosis in the chronic phase but has no effect on the acute inflammatory response or on the onset of pulmonary fibrosis. The antifibrotic effect of pranlukast may be exhibited by antagonizing the direct profibrotic effect of CysLTs, without affecting the expression of other profibrotic cytokines such as TGF-β1 and TNF-α, and also by decreasing the production of CysLTs and LTB₄.

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Section: Discussionmentioning

confidence: 65%

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

Shimbori

Shiota²,

Okunishi³

2012

Int Arch Allergy Immunol

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“…A protective effect was also observed after the administration of a 5-LOX inhibitor (zileuton) [33]. Moreover, it has been shown the LTB4 receptor antagonist diminishes the development of bleomycin-induced pulmonary fibrosis in mice by decreasing inflammation, hydroxyproline content and expression of TGF-beta, IL-6, and IL-13 in the lungs [34].…”

Section: Leukotrienes and Systemic Sclerosismentioning

confidence: 81%

The role of leukotrienes in the pathogenesis of systemic sclerosis

Chwieśko-Minarowska

Kowal

Bielecki

et al. 2012

Folia Histochem Cytobiol.

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Systemic sclerosis (SSc, scleroderma) is an autoimmune disease characterized by widespread vascular injury and progressive fibrosis of the skin and internal organs. SSc-related involvement of the lungs, heart, kidneys and/or the gastrointestinal system accounts for the increased mortality of scleroderma patients. Despite the progress which has recently been made in this field, the treatment of SSc is still unsatisfactory due to the low efficacy and/or high toxicity of available therapies. Leukotrienes are a family of lipid mediators synthesized from arachidonic acid in a process mediated by 5-lipoxygenase; they include leukotriene B4 and a group of cysteinyl leukotrienes: C4, D4, and E4. Leukotrienes play an important role in the regulation of all the processes vital to the pathogenesis of SSc, namely inflammation, vascular function and connective tissue remodeling. The available data suggests that an excessive synthesis of leukotrienes may contribute to the development and progression of SSc. Accordingly, blockade of leukotriene pathways appears to be a new, promising target for the treatment of

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“…Thus, they are capable of transcellular leukotriene synthesis when provided with an external source of the intermediate metabolite LTA4, such as infiltrating leukocyte LTA4 [189] (Figure 2). Leukotrienes have been shown to be involved in fibroblast-associated non-cancerous pathologies such as hepatic and pulmonary fibrosis [190,191]. There is currently no research in the area of leukotriene synthesis and CAFs, however, Medina et al demonstrated that fibroblasts which had been transformed by simian virus 40 (SV-40) had significantly increased LTA4 hydrolase activity and produced more LTB4 compared to normal fibroblasts [192].…”

Section: 5-lipoxygenase and Cancer-associated Fibroblastsmentioning

confidence: 99%

Cross-Talk between Cancer Cells and the Tumour Microenvironment: The Role of the 5-Lipoxygenase Pathway

Moore

Pidgeon

2017

IJMS

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5-lipoxygenase is an enzyme responsible for the synthesis of a range of bioactive lipids signalling molecules known collectively as eicosanoids. 5-lipoxygenase metabolites such as 5-hydroxyeicosatetraenoic acid (5-HETE) and a number of leukotrienes are mostly derived from arachidonic acid and have been shown to be lipid mediators of inflammation in different pathological states including cancer. Upregulated 5-lipoxygenase expression and metabolite production is found in a number of cancer types and has been shown to be associated with increased tumorigenesis. 5-lipoxygenase activity is present in a number of diverse cell types of the immune system and connective tissue. In this review, we discuss potential routes through which cancer cells may utilise the 5-lipoxygenase pathway to interact with the tumour microenvironment during the development and progression of a tumour. Furthermore, immune-derived 5-lipoxygenase signalling can drive both pro- and anti-tumour effects depending on the immune cell subtype and an overview of evidence for these opposing effects is presented.

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Effects of a leukotriene B4 receptor antagonist on bleomycin-induced pulmonary fibrosis

Cited by 48 publications

References 28 publications

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

The role of leukotrienes in the pathogenesis of systemic sclerosis

Cross-Talk between Cancer Cells and the Tumour Microenvironment: The Role of the 5-Lipoxygenase Pathway

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