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

Authors
Marcella M. MascarenhasRegina M. DayCristiaan D. OchoaWon-Il ChoiLunyin YuBin OuyangHari G. GargCharles A. HalesDeborah A. Quinn
Department
Dept. of Internal Medicine (내과학)
Issue Date
2004
Citation
American Journal of Respiratory and Critical Care Medicine, Vol.30(1) : 51-60, 2004
ISSN
1073-449X
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
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/34924
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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Full Text
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
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