Am. J. Respir. Cell Mol. Biol., Volume 22, Number 6, June, 2000 685-692

Effects of TNF- on Expression of ICAM-1 in Human Airway Epithelial Cells In Vitro
Signaling Pathways Controlling Surface and Gene Expression

Thomas M. Krunkosky, Bernard M. Fischer, Linda D. Martin, Neil Jones, Nancy J. Akley, and Kenneth B. Adler

Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh; and Inspire Pharmaceuticals, Incorporated, Durham, North Carolina

Signaling pathways associated with tumor necrosis factor (TNF)--induced intercellular adhesion molecule 1 (ICAM-1) surface and gene expression were investigated in well differentiated normal human bronchial epithelial (NHBE) cells in air-liquid interface primary culture. Cells were exposed to human recombinant TNF- (hrTNF-; 0.015 to 150 ng/ml [specific activity, 2.86 × 10⁷ U/mg]). TNF- enhanced ICAM-1 surface expression (measured by flow cytometry) and steady-state messenger RNA (mRNA) levels (assessed by Northern hybridization) in concentration- and time-dependent manners. TNF--induced ICAM-1 surface and gene expression were both blocked by the RNA polymerase II inhibitor actinomycin D (0.1 µg/ml), and surface expression was attenuated by a neutralizing monoclonal antibody directed against the TNF- receptor p55 (TNF-RI). The intracellular signaling pathway leading to enhanced expression appeared to involve activation of a phospholipase C that hydrolyzes phosphatidylcholine (PC-PLC) because D609, a specific PC-PLC inhibitor, attenuated TNF--induced increases in production of diacyl-glycerol (DAG), a hydrolysis product of PC-PLC, and also attenuated TNF- enhancement of ICAM-1 surface and gene expression. Because DAG formed by action of PC-PLC can activate protein kinase C (PKC), involvement of PKC was investigated. The specific PKC inhibitor calphostin C blocked both surface and gene expression of ICAM-1 in response to TNF- in a concentration-dependent manner. Finally, TNF- stimulated binding of p65 and/or c-rel complexes to the nuclear factor (NF)-B consensus binding site found on the ICAM-1 promoter, and binding of these complexes was inhibited by D609. The results support the following pathway, whereby TNF- enhances expression of ICAM-1 in NHBE cells: TNF-  TNF-RI  PC-PLC  DAG  PKC  (NF-B?)  ICAM-1 mRNA  ICAM-1 surface expression.

This article has been cited by other articles:

				R. Balder, T. M. Krunkosky, C. Q. Nguyen, L. Feezel, and E. R. Lafontaine Hag Mediates Adherence of Moraxella catarrhalis to Ciliated Human Airway Cells Infect. Immun., October 1, 2009; 77(10): 4597 - 4608. [Abstract] [Full Text] [PDF]

				M. V. Bautista, Y. Chen, V. S. Ivanova, M. K. Rahimi, A. M. Watson, and M. C. Rose IL-8 Regulates Mucin Gene Expression at the Posttranscriptional Level in Lung Epithelial Cells J. Immunol., August 1, 2009; 183(3): 2159 - 2166. [Abstract] [Full Text] [PDF]

				S. Ahmad, A. Ahmad, E. S. Dremina, V. S. Sharov, X. Guo, T. N. Jones, J. E. Loader, J. R. Tatreau, A.-L. Perraud, C. Schoneich, et al. Bcl-2 Suppresses Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase Expression in Cystic Fibrosis Airways: Role in Oxidant-mediated Cell Death Am. J. Respir. Crit. Care Med., May 1, 2009; 179(9): 816 - 826. [Abstract] [Full Text] [PDF]

				M. Kesimer, S. Kirkham, R. J. Pickles, A. G. Henderson, N. E. Alexis, G. DeMaria, D. Knight, D. J. Thornton, and J. K. Sheehan Tracheobronchial air-liquid interface cell culture: a model for innate mucosal defense of the upper airways? Am J Physiol Lung Cell Mol Physiol, January 1, 2009; 296(1): L92 - L100. [Abstract] [Full Text] [PDF]

				J. Park, S. Fang, A. L. Crews, K.-W. Lin, and K. B. Adler MARCKS Regulation of Mucin Secretion by Airway Epithelium in Vitro: Interaction with Chaperones Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 68 - 76. [Abstract] [Full Text] [PDF]

				X. Dai, K. Sayama, M. Tohyama, Y. Shirakata, L. Yang, S. Hirakawa, S. Tokumaru, and K. Hashimoto The NF-{kappa}B, p38 MAPK and STAT1 pathways differentially regulate the dsRNA-mediated innate immune responses of epidermal keratinocytes Int. Immunol., July 1, 2008; 20(7): 901 - 909. [Abstract] [Full Text] [PDF]

				W. Burkhardt, P. Koehne, H. Wissel, S. Graf, H. Proquitte, R. R. Wauer, and M. Rudiger Intratracheal perfluorocarbons diminish LPS-induced increase in systemic TNF-{alpha} Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1043 - L1048. [Abstract] [Full Text] [PDF]

				B. Jakiela, R. Brockman-Schneider, S. Amineva, W.-M. Lee, and J. E. Gern Basal Cells of Differentiated Bronchial Epithelium Are More Susceptible to Rhinovirus Infection Am. J. Respir. Cell Mol. Biol., May 1, 2008; 38(5): 517 - 523. [Abstract] [Full Text] [PDF]

				H. Slevogt, L. Maqami, K. Vardarowa, W. Beermann, A. C. Hocke, J. Eitel, B. Schmeck, A. Weimann, B. Opitz, S. Hippenstiel, et al. Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms Eur. Respir. J., April 1, 2008; 31(4): 725 - 735. [Abstract] [Full Text] [PDF]

				J.-A. Park, A. L. Crews, W. R. Lampe, S. Fang, J. Park, and K. B. Adler Protein Kinase C{delta} Regulates Airway Mucin Secretion via Phosphorylation of MARCKS Protein Am. J. Pathol., December 1, 2007; 171(6): 1822 - 1830. [Abstract] [Full Text] [PDF]

				G. Cheng, Z. Shao, B. Chaudhari, and D. K. Agrawal Involvement of chloride channels in TGF-beta1-induced apoptosis of human bronchial epithelial cells Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1339 - L1347. [Abstract] [Full Text] [PDF]

				D. C. Newcomb, U. S. Sajjan, D. R. Nagarkar, A. M. Goldsmith, J. K. Bentley, and M. B. Hershenson Cooperative effects of rhinovirus and TNF-{alpha} on airway epithelial cell chemokine expression Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L1021 - L1028. [Abstract] [Full Text] [PDF]

				B. M. Fischer, S. Zheng, R. Fan, and J. A. Voynow Neutrophil elastase inhibition of cell cycle progression in airway epithelial cells in vitro is mediated by p27kip1 Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L762 - L768. [Abstract] [Full Text] [PDF]

				H. Liu, H. Zhang, and H. J. Forman Silica Induces Macrophage Cytokines through Phosphatidylcholine-Specific Phospholipase C with Hydrogen Peroxide Am. J. Respir. Cell Mol. Biol., May 1, 2007; 36(5): 594 - 599. [Abstract] [Full Text] [PDF]

				Y. Chen, T. J. Nickola, N. L. DiFronzo, A. M. Colberg-Poley, and M. C. Rose Dexamethasone-Mediated Repression of MUC5AC Gene Expression in Human Lung Epithelial Cells Am. J. Respir. Cell Mol. Biol., March 1, 2006; 34(3): 338 - 347. [Abstract] [Full Text] [PDF]

				B. N. Chorley, Y. Li, S. Fang, J.-A. Park, and K. B. Adler (R)-Albuterol Elicits Antiinflammatory Effects in Human Airway Epithelial Cells via iNOS Am. J. Respir. Cell Mol. Biol., January 1, 2006; 34(1): 119 - 127. [Abstract] [Full Text] [PDF]

				W. Matsuyama, H. Mitsuyama, M. Watanabe, K.-i. Oonakahara, I. Higashimoto, M. Osame, and K. Arimura Effects of Omega-3 Polyunsaturated Fatty Acids on Inflammatory Markers in COPD Chest, December 1, 2005; 128(6): 3817 - 3827. [Abstract] [Full Text] [PDF]

				T. M. Krunkosky, K. Maruo, J. Potempa, C. L. Jarrett, and J. Travis Inhibition of Tumor Necrosis Factor-{alpha}-Induced RANTES Secretion by Alkaline Protease in A549 Cells Am. J. Respir. Cell Mol. Biol., November 1, 2005; 33(5): 483 - 489. [Abstract] [Full Text] [PDF]

				J.-A. Park, F. He, L. D. Martin, Y. Li, B. N. Chorley, and K. B. Adler Human Neutrophil Elastase Induces Hypersecretion of Mucin from Well-Differentiated Human Bronchial Epithelial Cells in Vitro via a Protein Kinase C{delta}-Mediated Mechanism Am. J. Pathol., September 1, 2005; 167(3): 651 - 661. [Abstract] [Full Text] [PDF]

				Y. Katagiri, T. Ito, S. Saino-Saito, Y. Hozumi, A. Suwabe, K. Otake, M. Sata, H. Kondo, F. Sakane, H. Kanoh, et al. Expression and localization of diacylglycerol kinase isozymes and enzymatic features in rat lung Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1171 - L1178. [Abstract] [Full Text] [PDF]

				T. Mathisen, S. G. Von Essen, T. A. Wyatt, and D. J. Romberger Hog barn dust extract augments lymphocyte adhesion to human airway epithelial cells J Appl Physiol, May 1, 2004; 96(5): 1738 - 1744. [Abstract] [Full Text] [PDF]

				J. Tamaoki The Effects of Macrolides on Inflammatory Cells Chest, February 1, 2004; 125 (2009): 41S - 51S. [Abstract] [Full Text] [PDF]

				S. P. Umland, C. G. Garlisi, H. Shah, Y. Wan, J. Zou, K. E. Devito, W.-M. Huang, E. L. Gustafson, and R. Ralston Human ADAM33 Messenger RNA Expression Profile and Post-Transcriptional Regulation Am. J. Respir. Cell Mol. Biol., November 1, 2003; 29(5): 571 - 582. [Abstract] [Full Text]

				A. A. Floreani, T. A. Wyatt, J. Stoner, S. D. Sanderson, E. G. Thompson, D. Allen-Gipson, and A. J. Heires Smoke and C5a Induce Airway Epithelial Intercellular Adhesion Molecule-1 and Cell Adhesion Am. J. Respir. Cell Mol. Biol., October 1, 2003; 29(4): 472 - 482. [Abstract] [Full Text] [PDF]

				T. R. Meusel and F. Imani Viral Induction of Inflammatory Cytokines in Human Epithelial Cells Follows a p38 Mitogen-Activated Protein Kinase-Dependent but NF-{kappa}B-Independent Pathway J. Immunol., October 1, 2003; 171(7): 3768 - 3774. [Abstract] [Full Text] [PDF]

				K. Page, J. Li, L. Zhou, S. Iasvoyskaia, K. C. Corbit, J.-W. Soh, I. B. Weinstein, A. R. Brasier, A. Lin, and M. B. Hershenson Regulation of Airway Epithelial Cell NF-{kappa}B-Dependent Gene Expression by Protein Kinase C{delta} J. Immunol., June 1, 2003; 170(11): 5681 - 5689. [Abstract] [Full Text] [PDF]

				P. J. Kolodziejski, A. Musial, J.-S. Koo, and N. T. Eissa Ubiquitination of inducible nitric oxide synthase is required for its degradation PNAS, September 17, 2002; 99(19): 12315 - 12320. [Abstract] [Full Text] [PDF]

				K. Wolf, C. Schulz, G.A.J. Riegger, and M. Pfeifer Tumour necrosis factor-{alpha} induced CD70 and interleukin-7R mRNA expression in BEAS-2B cells Eur. Respir. J., August 1, 2002; 20(2): 369 - 375. [Abstract] [Full Text] [PDF]

				T. R. Meusel, K. E. Kehoe, and F. Imani Protein Kinase R Regulates Double-Stranded RNA Induction of TNF-{alpha} But Not IL-1{beta} mRNA in Human Epithelial Cells J. Immunol., June 15, 2002; 168(12): 6429 - 6435. [Abstract] [Full Text] [PDF]

				B. M. Fischer and J. A. Voynow Neutrophil Elastase Induces MUC5AC Gene Expression in Airway Epithelium via a Pathway Involving Reactive Oxygen Species Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 447 - 452. [Abstract] [Full Text] [PDF]

				P. Delmotte, S. Degroote, J.-J. Lafitte, G. Lamblin, J.-M. Perini, and P. Roussel Tumor Necrosis Factor alpha Increases the Expression of Glycosyltransferases and Sulfotransferases Responsible for the Biosynthesis of Sialylated and/or Sulfated Lewis x Epitopes in the Human Bronchial Mucosa J. Biol. Chem., January 4, 2002; 277(1): 424 - 431. [Abstract] [Full Text]

				B. W. Booth, K. B. Adler, J. C. Bonner, F. Tournier, and L. D. Martin Interleukin-13 Induces Proliferation of Human Airway Epithelial Cells In Vitro via a Mechanism Mediated by Transforming Growth Factor-alpha Am. J. Respir. Cell Mol. Biol., December 1, 2001; 25(6): 739 - 743. [Abstract] [Full Text] [PDF]

				K. B. Adler and Y. Li Airway Epithelium and Mucus . Intracellular Signaling Pathways for Gene Expression and Secretion Am. J. Respir. Cell Mol. Biol., October 1, 2001; 25(4): 397 - 400. [Full Text] [PDF]

				Y. Song, L. Ao, C. D. Raeburn, C. M. Calkins, E. Abraham, A. H. Harken, and X. Meng A low level of TNF-{alpha} mediates hemorrhage-induced acute lung injury via p55 TNF receptor Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L677 - L684. [Abstract] [Full Text] [PDF]

				M. Chanson, P.-Y. Berclaz, I. Scerri, T. Dudez, K. Wernke-Dollries, L. Pizurki, A. Pavirani, M. A. Fiedler, and S. Suter Regulation of Gap Junctional Communication by a Pro-Inflammatory Cytokine in Cystic Fibrosis Transmembrane Conductance Regulator-Expressing but Not Cystic Fibrosis Airway Cells Am. J. Pathol., May 1, 2001; 158(5): 1775 - 1784. [Abstract] [Full Text] [PDF]

				Y. Li, L. D. Martin, G. Spizz, and K. B. Adler MARCKS Protein Is a Key Molecule Regulating Mucin Secretion by Human Airway Epithelial Cells in Vitro J. Biol. Chem., October 26, 2001; 276(44): 40982 - 40990. [Abstract] [Full Text] [PDF]

				J. Fan, R. S. Frey, A. Rahman, and A. B. Malik Role of Neutrophil NADPH Oxidase in the Mechanism of Tumor Necrosis Factor-alpha -induced NF-kappa B Activation and Intercellular Adhesion Molecule-1 Expression in Endothelial Cells J. Biol. Chem., January 25, 2002; 277(5): 3404 - 3411. [Abstract] [Full Text] [PDF]