Short communication
Vol. 141 No. 4142 (2011)
Low molecular weight hyaluronan, via AP-1 and NF-κB signalling, induces IL-8 in transformed bronchial epithelial cells
- CD Ochoa
- HG Garg
- CA Hales
- DA Quinn
Summary
QUESTIONS UNDER STUDY: New evidence demonstrated that high tidal volume mechanical ventilation results in substantial bronchial airway mechanical strain. In addition, high tidal volume mechanical ventilation has been shown to increase IL-8 production in a mechanism mediated, at least in part, by low molecular weight hyaluronan (LWM-HA). In the present study, it was investigated whether LMW-HA synthesised in the lung, in response to cyclic stretch, increased IL-8 production in the bronchial epithelium.
METHODS: This question was approached by stimulating a transformed human bronchial epithelial cell line with LMW-HA isolated from stretched human lung fibroblasts and probed for the activation of extracellular signal-regulated kinase pathways.
RESULTS: LMW-HA increased IL-8 secretion in transformed bronchial epithelial cells. Additionally, LMW-HA augmented the levels of phospho c-Jun NH2-terminal kinase (JNK) and phospho extracellular signal-regulated kinase 1/2 (ERK1/2), and also mobilised nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) from the cytoplasm to the nucleus. The inhibition of JNK, ERK1/2 and NF-κB blocked IL-8 secretion in response to LMW-HA.
CONCLUSION: The data suggest that LMW-HA produced by lung fibroblasts in response to cyclic stretch increases the secretion of IL-8 in transformed bronchial epithelial cells via AP-1 and NF-κB signalling pathways. These findings support the hypothesis that LMW-HA plays an active role in acute lung inflammation triggered by mechanical strain.
References
- Mascarenhas MM, Day RM, Ochoa CD, Choi WI, Yu L, Ouyang B, et al. Low molecular weight hyaluronan from stretched lung enhances interleukin-8 expression. Am J Respir Cell Mol Biol. 2004;30(1):51–60.
- Liu YY, Lee CH, Dedaj R, Zhao H, Mrabat H, Sheidlin A, et al. High-molecular-weight hyaluronan – a possible new treatment for sepsis-induced lung injury: a preclinical study in mechanically ventilated rats. Crit Care. 2008;12(4):R102.
- Laurent TC, Fraser JR, Laurent UB, Engstrom-Laurent A. Hyaluronan in inflammatory joint disease. Acta Orthop Scand Suppl. 1995;266:116–20.
- Garg HG, Quinn DA, Mascarenhas MM, Hales CA. Hyaluronan in Ventilator-Induced Lung Injury. In Chemistry and Biology of Hyaluronan. Edited by Garg HG, Hales CA. Boston: Elsevier; 2004:271.
- Bracke KR, Dentener MA, Papakonstantinou E, Vernooy JH, Demoor T, Pauwels NS, et al. Enhanced Deposition of Low Weight Hyaluronan in Lungs of Cigarette Smoke-Exposed Mice. Am J Respir Cell Mol Biol. 2009.
- Bai KJ, Spicer AP, Mascarenhas MM, Yu L, Ochoa CD, Garg HG, et al. The role of hyaluronan synthase 3 in ventilator-induced lung injury. Am J Respir Crit Care Med. 2005;172(1):92–8.
- Nettelbladt O, Hallgren R. Hyaluronan (hyaluronic acid) in bronchoalveolar lavage fluid during the development of bleomycin-induced alveolitis in the rat. Am Rev Respir Dis. 1989;140(4):1028–32.
- Zaman A, Cui Z, Foley JP, Zhao H, Grimm PC, Delisser HM, et al. Expression and role of the hyaluronan receptor RHAMM in inflammation after bleomycin injury. Am J Respir Cell Mol Biol. 2005;33(5):447–54.
- Boodoo S, Spannhake EW, Powell JD, Horton MR. Differential regulation of hyaluronan-induced IL-8 and IP-10 in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2006;291(3):L479–86.
- Horton MR, Burdick MD, Strieter RM, Bao C, Noble PW. Regulation of hyaluronan-induced chemokine gene expression by IL-10 and IFN-gamma in mouse macrophages. J Immunol. 1998;160(6):3023–30.
- Horton MR, Shapiro S, Bao C, Lowenstein CJ, Noble PW. Induction and regulation of macrophage metalloelastase by hyaluronan fragments in mouse macrophages. J Immunol. 1999;162(7):4171–6.
- Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y, et al. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat Med. 2005;11(11):1173–9.
- Sinclair SE, Molthen RC, Haworth ST, Dawson CA, Waters CM. Airway strain during mechanical ventilation in an intact animal model. Am J Respir Crit Care Med. 2007;176(8):786–94.
- Schaffer JL, Rizen M, L’Italien GJ, Benbrahim A, Megerman J, Gerstenfeld LC, et al. Device for the application of a dynamic biaxially uniform and isotropic strain to a flexible cell culture membrane. J Orthop Res. 1994;12(5):709–19.
- Li LF, Ouyang B, Choukroun G, Matyal R, Mascarenhas M, Jafari B, et al. Stretch-induced IL-8 depends on c-Jun NH2-terminal and nuclear factor-kappaB-inducing kinases. Am J Physiol Lung Cell Mol Physiol. 2003;285(2):L464–75.
- Ochoa CD, Baker H, Hasak S, Matyal R, Salam A, Hales CA, et al. Cyclic stretch affects pulmonary endothelial cell control of pulmonary smooth muscle cell growth. Am J Respir Cell Mol Biol. 2008;39(1):105–12.
- Ishibashi Y, Nishikawa A. Role of nuclear factor-kappa B in the regulation of intercellular adhesion molecule 1 after infection of human bronchial epithelial cells by Bordetella pertussis. Microb Pathog. 2003;35(4):169–77.
- Oeckler RA, Hubmayr RD. Ventilator-associated lung injury: a search for better therapeutic targets. Eur Respir J. 2007;30(6):1216–26.
- Parker JC, Townsley MI, Rippe B, Taylor AE, Thigpen J. Increased microvascular permeability in dog lungs due to high peak airway pressures. J Appl Physiol. 1984;57(6):1809–16.
- Gattinoni L, Pesenti A, Avalli L, Rossi F, Bombino M. Pressure-volume curve of total respiratory system in acute respiratory failure. Computed tomographic scan study. Am Rev Respir Dis. 1987;136(3):730–6.
- Dreyfuss D, Soler P, Basset G, Saumon G. High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis. 1988;137(5):1159–64.
- Petrucci N, Iacovelli W. Lung protective ventilation strategy for the acute respiratory distress syndrome. Cochrane Database Syst Rev 2007, (3)(3):CD003844.
- Yu L, Quinn DA, Garg HG, Hales CA. Cyclin-dependent kinase inhibitor p27Kip1, but not p21WAF1/Cip1, is required for inhibition of hypoxia-induced pulmonary hypertension and remodeling by heparin in mice. Circ Res. 2005;97(9):937–45.
- Thompson BT, Spence CR, Janssens SP, Joseph PM, Hales CA. Inhibition of hypoxic pulmonary hypertension by heparins of differing in vitro antiproliferative potency. Am J Respir Crit Care Med. 1994;149(6):1512–7.
- Hassoun PM, Thompson BT, Steigman D, Hales CA. Effect of heparin and warfarin on chronic hypoxic pulmonary hypertension and vascular remodeling in the guinea pig. Am Rev Respir Dis. 1989;139(3):763–8.
- Anderson Bray B. Hyaluronan in the Pulmonary Alveolus and Interstitium. In Chemistry and Biology of Hyaluronan. Edited by Garg GA, Hales CA. Boston: Elsevier; 2004:247.
- Spicer AP, Augustine ML, McDonald JA. Molecular cloning and characterization of a putative mouse hyaluronan synthase. J Biol Chem. 1996;271(38):23400–6.
- Shyjan AM, Heldin P, Butcher EC, Yoshino T, Briskin MJ. Functional cloning of the cDNA for a human hyaluronan synthase. J Biol Chem. 1996;271(38):23395–9.
- Watanabe K, Yamaguchi Y. Molecular identification of a putative human hyaluronan synthase. J Biol Chem. 1996;271(38):22945–8.
- Johnson P, Ruffell B. CD44 and its role in inflammation and inflammatory diseases. Inflamm Allergy Drug Targets. 2009;8(3):208–20.
- Day RM, Mascarenhas M. Signal Transduction Associated with Hyaluronan. In Chemistry and Biology of Hyaluronan. Edited by Garg GA, Hales CA. Boston: Elsevier; 2004:153.
- McDonald B, McAvoy EF, Lam F, Gill V, de la Motte C, Savani RC, et al. Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. J Exp Med. 2008;205(4):915–27.
- Li LF, Yu L, Quinn DA. Ventilation-induced neutrophil infiltration depends on c-Jun N-terminal kinase. Am J Respir Crit Care Med. 2004;169(4):518–24.
- Kanda T, Yokosuka O, Nagao K, Saisho H. State of hepatitis C viral replication enhances activation of NF-κB- and AP-1-signaling induced by hepatitis B virus X. Cancer Lett. 2006;234(2):143–8.
- Cruz MT, Goncalo M, Figueiredo A, Carvalho AP, Duarte CB, Lopes MC. Contact sensitizer nickel sulfate activates the transcription factors NF-κB and AP-1 and increases the expression of nitric oxide synthase in a skin dendritic cell line. Exp Dermatol. 2004;13(1):18–26.
- Seidel P, Merfort I, Tamm M, Roth M. Inhibition of NF-kappaB and AP-1 by dimethylfumarate correlates with down-regulated IL-6 secretion and proliferation in human lung fibroblasts. Swiss Med Wkly. 2010;140:w13132.
- Yasumoto K, Okamoto S, Mukaida N, Murakami S, Mai M, Matsushima K. Tumor necrosis factor alpha and interferon gamma synergistically induce interleukin 8 production in a human gastric cancer cell line through acting concurrently on AP-1 and NF-κB-like binding sites of the interleukin 8 gene. J Biol Chem. 1992;267(31):22506–11.