Leukotriene D(4) enhances the function of endothelin-1-primed fibroblasts.
Airway inflammation is accompanied by structural changes, termed remodeling, that lead to lung dysfunction over the long term. Although both endothelin-1 (ET-1) and cysteinyl leukotrienes (CysLTs) appear to be involved in airway remodeling in several lung diseases, how these molecules interact remains largely unknown. In this study, we examined the effects of leukotriene (LT) D(4) on the function of ET-1-primed fibroblasts. ET-1 at 10(-7) M up-regulated the expression of the CysLT receptors at both the mRNA and protein levels in human lung fibroblasts. LTD(4) enhanced matrix metalloproteinase-2 and pro-collagen production, and alpha-smooth muscle actin expression of ET-1-primed fibroblasts, but had little or no effect on unprimed fibroblasts. The CysLT1 receptor antagonist montelukast completely abrogated the effects of LTD(4). Our data suggested that LTD(4) may act as a precipitating factor during ET-1-mediated airway remodeling and that CysLT1 receptor antagonists may have a role in preventing aberrant extracellular matrix degradation.
Tokuriki
Shuko
S
Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida-Gun, Fukui, Japan.
Ohshima
Yusei
Y
Yamada
Akiko
A
Ohta
Naoko
N
Tsukahara
Hirokazu
H
Mayumi
Mitsufumi
M
D000085:Acetates / Q000494:pharmacology; D000199:Actins / Q000187:drug effects / Q000378:metabolism; D003521:Cyclopropanes; D019332:Endothelin-1 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017998:Leukotriene D4 / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D011347:Procollagen / Q000187:drug effects / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018077:Receptors, Leukotriene / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013440:Sulfides; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1 / Q000187:drug effects / Q000378:metabolism
D000085:Acetates; D000199:Actins; D003521:Cyclopropanes; D019332:Endothelin-1; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D010446:Peptide Fragments; D011347:Procollagen; D011804:Quinolines; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; D013440:Sulfides; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1; C042813:procollagen type I carboxy terminal peptide; D017998:Leukotriene D4; D020782:Matrix Metalloproteinases; C083169:leukotriene D4 receptor; C093875:montelukast