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Cited by 51Asthma and respiratory diseasesEicosanoids and Hypertension PharmacologyTGF-β signaling in diseases

Leukotriene D4 stimulates collagen production from myofibroblasts transformed by TGF-β

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Asakura, Takuma, Ishii, Yoshiki, Chibana, Kazuyuki, Fukuda, Takeshi·2004·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2004.04.037
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Abstract

Background Airway remodeling has an important role in the pathogenesis of bronchial asthma. Many mediators that influence the pathophysiology of bronchial asthma, especially cysteinyl leukotrienes (CysLTs) and TGF-beta1, are involved in airway remodeling. Objective To know whether TGF-beta1 alters fibroblast responsiveness to CysLTs, we examined the effects of leukotriene (LT) D4 on collagen production from fibroblasts and from myofibroblasts transformed by TGF-beta1. We also examined whether TGF-beta1 upregulates CysLT1 receptor (CysLT1R) expression in fibroblasts. Methods Concentrations of procollagen in the human fetal lung fibroblast (HFL) 1 cell supernatant were measured by using an enzyme immunoassay kit in the presence or absence of various concentrations of LTD4, TGF-beta1, CysLT1R antagonist, or some combination of these. The mRNA expression of CysLT1R and alpha-smooth muscle actin as a marker of myofibroblasts was measured by means of real-time PCR. Furthermore, protein expression of CysLT1R on fibroblasts was measured by means of flow cytometric analysis. Results TGF-beta1 stimulated collagen production from HFL-1 cells, but LTD4 alone did not. LTD4 in combination with TGF-beta1 increased collagen production compared with TGF-beta1 alone. Real-time PCR showed that stimulation with TGF-beta1 significantly upregulated CysLT1R and alpha-smooth muscle actin mRNA expression in HFL-1 cells. Conclusions LTD4 increased collagen production by upregulating CysLT1R induced by TGF-beta1. In the TGF-beta-rich milieu, activated myofibroblasts expressing CysLT1R can respond to CysLTs and produce large amounts of extracellular matrix, thereby contributing to airway remodeling. These data suggest that treatment with leukotriene receptor antagonists might prevent airway remodeling in patients with asthma.

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  • The number of myofibroblasts is significantly reduced in THS-exposed mouse wounds.

    “The decrease in the level of collagen deposition observed at day 7 post-injury in the THSexposed mouse wounds correlates with the significantly reduced number of myofibroblasts, cells that effectively produce fibrillar collagen [39].”

    From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [39]

  • Collagen deposition is decreased at day 7 post-injury in THS-exposed mouse wounds.

    “The decrease in the level of collagen deposition observed at day 7 post-injury in the THSexposed mouse wounds correlates with the significantly reduced number of myofibroblasts, cells that effectively produce fibrillar collagen [39].”

    From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [39]

  • The decrease in collagen deposition at day 7 in THS-exposed mouse wounds correlates with the reduced number of myofibroblasts.

    “The decrease in the level of collagen deposition observed at day 7 post-injury in the THSexposed mouse wounds correlates with the significantly reduced number of myofibroblasts, cells that effectively produce fibrillar collagen [39].”

    From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [39]

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Cited by

Sorted by citations

Authors
Asakura, T., Ishii, Y., Chibana, K., & Fukuda, T.
Affiliations
Dokkyo University (JP)
Corresponding author
Ishii, Yoshiki
ORCID
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2004-08
Volume
114
Issue
2
Pages
310-315
ISSN
0091-6749 (ISSN-L)
DOI
10.1016/j.jaci.2004.04.037
OpenAlex
W2017376355
Cited by
51
References
0
Citations by year
2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 3 · 2013: 2 · 2012: 6
FWCI
1.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
leukotriene D4, cysteinyl leukotrienes, TGF-β1, myofibroblasts, collagen synthesis, airway remodeling, asthma, CysLT1 receptor, alpha-smooth muscle actin, fibroblasts, leukotriene receptor antagonists, extracellular matrix
MeSH terms
Cell Division, Cells, Cultured, Fibroblasts, Humans, Membrane Proteins, Peptide Fragments, Procollagen, RNA, Messenger, Transforming Growth Factor beta, Leukotriene D4, Receptors, Leukotriene

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