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Low Molecular Weight Hyaluronan from Stretched Lung Enhances Interleukin-8 Expression

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Author(s)
Marcella M. MascarenhasRegina M. DayCristiaan D. OchoaWon-Il ChoiLunyin YuBin OuyangHari G. GargCharles A. HalesDeborah A. Quinn
Keimyung Author(s)
Choi, Won Il
Department
Dept. of Internal Medicine (내과학)
Journal Title
American Journal of Respiratory and Critical Care Medicine
Issued Date
2004
Volume
30
Issue
1
Abstract
Mechanical ventilation has been shown to cause ventilator-induced lung injury (VILI), probably by overdistending or stretching the lung. Hyaluronan (HA), a component of the extracellular matrix, in low molecular weight (LMW) forms has been shown to induce cytokine production. LMW HA is produced by hyaluronan synthase 3 (HAS 3). We found that HAS 3 mRNA expression was upregulated and that LMW HA accumulated in an animal model of VILI. We hypothesized that stretch-induced LMW HA production that causes cytokine release in VILI was dependent on HAS 3 mRNA expression. We explored this hypothesis with in vitro lung cell stretch. Cell stretch induced HAS 3 mRNA expression and LMW HA in fibroblasts. Nonspecific inhibitors of HAS 3 (cyclohexamide and dexamethasone), a nonspecific inhibitor of protein tyrosine kinases (genistein), and a janus kinase 2 inhibitor (AG490) blocked stretch-induced HAS 3 expression and synthesis of LMW HA. Stretch-induced LMW HA from fibroblasts caused a significant dose-dependent increase in interleukin-8 production both in static and stretched epithelial cells. These results indicated that de novo synthesis of LMW HA was induced in lung fibroblasts by stretch via tyrosine kinase signaling pathways, and may play a role in augmenting induction of proinflammatory cytokines in VILI.

KEYWORDS: acute respiratory distress syndrome, ARDS, chondroitin sulfate, CS, extracellular matrix, ECM, extracellular signal–regulated kinase, ERK, hyaluronan, HA, hyaluronan synthase 3, HAS 3, Hanks' buffered saline solution, HBSS, high molecular weight, HMW, interleukin, IL, Janus kinase, JAK, low molecular weight, LMW, lipopolysaccharide, LPS, macrophage inflammatory protein, MIP, polymerase chain reaction, PCR, proteoglycans, PGs, reverse transcription, RT, ventilator-induced lung injury, VILI



Read More: http://www.atsjournals.org/doi/abs/10.1165/rcmb.2002-0167OC#.VoORTE8ayzk
Keimyung Author(s)(Kor)
최원일
Publisher
School of Medicine
Citation
Marcella M. Mascarenhas et al. (2004). Low Molecular Weight Hyaluronan from Stretched Lung Enhances Interleukin-8 Expression. American Journal of Respiratory and Critical Care Medicine, 30(1), 51–60. doi: 10.1165/rcmb.2002-0167OC
Type
Article
ISSN
1073-449X
Source
https://www.atsjournals.org/doi/abs/10.1165/rcmb.2002-0167OC?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed
DOI
10.1165/rcmb.2002-0167OC
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34924
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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