Abstract
Inflammation is a central feature of many lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, fibrosing alveolitis and adult or acute respiratory distress syndrome (ARDS). The specific characteristics of the inflammatory response and the site of inflammation differ between these diseases, but all involve the recruitment and activation of inflammatory cells and chances in the structural cells of the lung. These diseases are characterized by an increased expression of many proteins involved in the complex inflammatory cascade. These inflammatory proteins include cytokines, enzymes that produce inflammatory mediators, receptors and adhesion molecules. The increased expression of most of these proteins is the result of increased gene transcription; many of the genes are not expressed in normal cells but are induced in certain cell types in these inflammatory diseases. Changes in gene transcription are regulated by transcription factors, which are proteins that bind to DNA. This suggests that transcription factors may play a key role in the pathophysiology of inflammatory diseases, because they regulate the increased gene expression that may underlie the acute and chronic inflammatory mechanisms that characterize these diseases. Corticosteroids are the most effective therapy in the long-term control of asthma and appear to reduce inflammation in asthmatic airways largely by inhibiting the transcription factors that regulate abnormal gene expression. Corticosteroids may also have a beneficial effect in other inflammatory lung diseases, although this is less marked than in asthma, indicating that different genes and transcription factors are involved.
Chapter PDF
Similar content being viewed by others
Keywords
- Glucocorticoid Receptor
- Respir Crit
- Inflammatory Lung Disease
- Basal Transcription Machinery
- Increase Gene Transcription
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
References
Hunter T, Karin M (1992) The regulation of transcription by phosphorylation. Cell 70: 375–387
Karin M, Smeal T (1993) Control of transcription factors by signal transduction pathways: the beginning of the end. Trends Biochem Sci 17: 418–422
Adcock IM, Barnes PJ (1996) Transcription factors. In: RG Crystal, JB West, WR Weibel, PJ Barnes (eds): The Lung: Scientific foundations. Lippincott-Raven, Philadelphia, 255–276
Latchman DS (1996) Transcription-factor mutations and disease. N Engl J Med 334: 28–33
Papavassilou AG (1995) Transcription factors. N Engl J Med 332: 45–47
Pfahl M (1993) Nuclear receptor/AP-1 interaction. Endocr Rev 14: 651–658
Tjian R, Maniatis T (1994) Transcriptional activation: a complex puzzle with few easy pieces. Cell 77: 5–8
Lalli E, Sassone-Corsi P (1994) Signal transduction and gene regulation: the nuclear response to cAMP. J Biol Chem 269: 17359–17362
Stein B, Baldwin AS (1993) Distinct mechanisms for the regulation of the interleukin-8 gene involve synergism and cooperativity between C/EBP and NF-κB. Mol Cell Biol 13: 7191–7198
Barnes PJ, Karin M (1997) Nuclear factor-κB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336: 1066–1071
Sen R, Baltimore D (1986) Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46: 705–716
Siebenlist U, Franzuso G, Brown R (1994) Structure, regulation and function of NF-κB. Annu Rev Cell Biol 10: 405–455
Baeuerle PA, Henkel T (1994) Function and activation of NF-κB in the immune system. Annu Rev Immunol 12: 141–179
Beg AA, Sha WC, Bronson RT, Ghosh S, Baltimore D (1995) Embroyonic lethality and liver degeneration in mice lacking the RelA component of NF-κB. Nature 376: 167–170
Sha WC, Liou HC, Tuomanen El, Baltimore D (1995) Targeted disruption of the p50 sub-unit of NF-κB leads to multifocal defects in immune responses. Cell 80: 321–330
Baldwin AS (1996) The NF-κB and IκB proteins: new discoveries and insights. Annu Rev Immunol 14: 649–681
Baeuerle PA, Baltimore D (1996) NF-κB: ten years on. Cell 87: 13–20
DiDonato J, Mercurio F, Rosette C, Wu-Li J, Suyang H, Ghosh S, Karin M (1996) Mapping of the inducible IκB phosphorylation sites that signal its ubiquitination and degradation. Mol Cell Biol 16: 1295–1304
Chen ZJ, Parent L, Maniatis T (1996) Site-specific phosphorylation of IκBα by a novel ubiquitination-dependent protein kinase activity. Cell 84: 853–862
Zandi E, Rothwarf DM, Delhase M, Hayakawa M, Karin M (1997) The IkB kinase complex (IKK) contains two kinase subunits, IKKα and IKKβ, necessary for IκB phosphorylation and NF-κB activation. Cell 91: 243–252
Eder J (1997) Tumour necrosis factor α and interleukin 1 signalling: do MAPKK kinases connect it all? Trends Pharmacol Sci 18: 319–322
Malinin NL, Boldin MP, Kovalenko AV, Wallach D (1997) MAP3K-related kinase is involved in NF-κB induction by TNF, CD95 and IL-1. Nature 385: 540–544
Lee FS, Hagler J, Chen ZJ, Maniatis T (1997) Activation of the IκB-α kinase complex by MEKK1, a kinase of the JNK pathway. Cell 88: 213–222
Arenzana-Seisdedos F, Thomson J, Rodriguez MS, Bachelerie F, Thomas D, Hay RT (1995) Inducible nuclear expression of newly synthesized IκB-α negatively regulates DNA binding and transcriptional activity of NF-κB. Mol Cell Biol 15: 2689–2696
Adcock IM, Barnes PJ (1996) Tumour necrosis factor alpha causes retention of activated glucocorticoid receptor within the cytoplasm of A549 cells. Biochem Biophys Res Commun 225: 1127–1132
Klement JF, Rice NR, Car BD et al. (1996) IκB-α deficiency results in a sustained NF-κ B response and severe widespread dermatitis in mice. Mol Cell Biol 16: 2341–2349
Thomspon JE, Phillips RJ, Erdjument-Bromage H, Tempst P, Ghosh S (1995) IκB-β regulates the persistent response in a biphasic activation of NF-κB. Cell 80: 573–582
Schreck R, Rieber P, Baeuerle PA (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-κB transcription factor and HIV-1. EMBO J 10: 2247–2258
Zhu Z, Tang W, Ray A et al. (1996) Rhinovirus stimulation of interleukin-6 in vivo and in vitro. Evidence for nuclear factor κB-dependent transcription activation. J Clin Invest 97: 421–430
Schreck R, Meier B, Männel DN, Dröge W, Baeuerle PA (1991) Dithiocarbamates as potent inhibitors of nuclear factor κB activation in intact cells. J Exp Med 175: 1181
Stein B, Baldwin AS, Ballard DW, Greene WC, Angel P, Herrlich P (1993) Cross-coupling of the NF-κB p65 and Fos/Jun transcription factors produces potential biological function. EMBO J 12: 3879–3891
Mukaido N, Morita M, Ishikawa Y, Rice N, Okamoto S, Kasahara T, Matsushima K (1994) Novel mechanisms of glucocorticoid-mediated gene repression: NF-κB is target for glucocorticoid-mediated IL-8 gene expression. J Biol Chem 269: 13289–13295
Nelson PJ, Kim HT, Manning WC, Goralski TJ, Krensky AM (1993) Genomic organisation and transcriptional regulation of the RANTES chemokine gene. J Immunol 151: 2601–2612
Ueda A, Okuda K, Shira A et al. (1994) NF-κB and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene. J Immunol 153: 2052–2063
Lilly CM, Nakamura H, Kesselman H et al. (1997) Expression of eotaxin by human lung epithelial cells: induction by cytokines and inhibition by glucocorticoids. J Clin Invest 99: 1767–1773
Xie Q, Kashiwarbara Y, Nathan C (1994) Role of transcription factor NF-κB/Rel in induction of nitric oxide synthase. J Biol Chem 269: 4705–4708
Yamamoto K, Arakawa T, Ueda N, Yamamoto S (1995) Transcriptional roles of nuclear factor κB and nuclear factor-interleukin 6 in the tumor necrosis-α-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells. J Biol Chem 270: 31315–31320
Newton R, Kuitert LM, Bergmann M, Adcock IM, Barnes PJ (1997) Evidence for involvement of NF-κB in the transcriptional control of COX-2 gene expression by IL-1β. Biochem Biophys Res Commun 237: 28–32
Iademarco MF, McQuillan JJ, Rosen GD, Dean DC (1995) Characterization of the promoter for vascular adhesion molecule-1 (VCAM-1). J Biol Chem 267: 16323–16329
Van De Stolpe A, Caldenhoven E, Stade BG, Koenderman L, Raaijmakers JA, Johnson JP, van Der Saag PT (1994) 12-O-Tetradecanoyl phorbol-13-acetate and tumor necrosis factor alpha-mediated induction of intercellular adhesion molecule-1 is inhibited by dexamethasone. Functional analysis of the human intercellular adhesion molecule-1 promoter. J Biol Chem 269: 6185–6192
Liu ZG, Hsu H, Goeddel DV, Karin M (1996) Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-κB activation prevents cell death. Cell 87: 565–576
Beg AA, Baltimore D (1996) An essential role for NF-κB in preventing TNF-α-induced cell death. Science 274: 782–784
Liu SF, Haddad E, Adcock IM et al. (1997) Inducible nitric oxide synthase after sensitization and allergen challenge of Brown Norway rat lung. Br J Pharmacol 121: 1241–1246
Haddad E-B, Liu SF, Salmon M, Robichaud A, Barnes PJ, Chung KF (1995) Expression of inducible nitric oxide synthase mRNA in Brown-Norway rats exposed to ozone: effect of dexamethasone. Eur J Pharmacol (Environ Toxicol Section) 293: 287–290
Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M (1995) Immunosuppression by glucocorticoids: inhibition of NF-κB activity through induction of IκB synthesis. Science 270: 286–290
Adcock IM, Brown CR, Kwon OJ, Barnes PJ (1994) Oxidative stress induces NF-κB DNA binding and inducible NOS mRNA in human epithelial cells. Biochem Biophys Res Commun 199: 1518–1524
Haddad E-B, Salmon M, Koto H, Barnes PJ, Adcock I, Chung KF (1996) Ozone induction of cytokine-induced neutrophil chemoattractant and nuclear factor-κB in rat lung: inhibition by corticosteroids. FEBS Lett 379: 265–268
Adcock IM, Brown CR, Gelder CM, Shirasaki H, Peters MJ, Barnes PJ (1995) The effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells. Am J Physiol 37: C331–C338
Jany B, Betz R, Schreck R (1995) Activation of the transcription factor NF-κB in human tracheobronchial epithelial cells by inflammatory stimuli. Eur Respir J 8: 387–391
Adock IM, Brown CR, Shirasaki H, Barnes PJ (1994) Effects of dexamethasone on cytokine and phorbol ester stimulated c-Fos and c-Jun DNA binding and gene expression in human lung. Eur Respir J 7: 2117–2123
Hart L, Krishnan VJ, Adcock IM, Barnes PJ, Chung KF (1998) Activation and localization of transcription factor nuclear factor-ÎşB in asthma. Am J Respir Crit Care Med, in press
Hamid Q, Springall DR, Riveros-Moreno V et al. (1993) Induction of nitric oxide synthase in asthma. Lancet 342: 1510–1513
Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R, Shinebourne E, Barnes PJ (1994) Increased nitric oxide in exhaled air of asthmatic patients. Lancet 343: 133–135
Collins PD, Marleau S, Griffiths-Johnson DA, Jose PJ, Williams TJ (1995) Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med 182: 1169–1174
Saleh D, Barnes PJ, Giaid A (1997) Increased production of the potent oxidant peroxynitrite in the lungs of patients with pulmonary fibrosis. Am J Respir Crit Care Med 155: 1763–1769
Paredi P, Kharitonov SA, Maziak W, du Bois RM, Barnes PJ (1997) Exhaled nitric oxide (NO) a possible marker for disease activity in patients with interstitial lung disease. Eur Respir J 10 (suppl 25): 158S
Simeonova PP, Luster MI (1996) Asbestos induction of nuclear transcription factors and interleukin 8 gene regulation. Am J Respir Cell Mol Biol 15: 787–795
Blackwell TS, Christman JW (1997) The role of nuclear factor-κB in cytokine gene regulation. Am J Respir Cell Mol Biol 17: 3–9
Blackwell TS, Blackwell TR, Holden EP, Christman BW, Christman JW (1996) In vivo antioxidant treatment suppresses nuclear factor-κB activation and neutrophilic lung inflammation. J Immunol 157: 1630–1637
Liu S, Adcock IM, Old RW, Barnes PJ, Evans TW (1993) Lipopolysaccharide treatment in vivo induces widespread expression of inducible nitric oxide synthase mRNA. Biochem Biophys Res Commun 196: 1208–1213
Schwartz MD, Moore EE, Moore FA, Shenkar R, Moine P, Haenel JB, Abraham E (1996) Nuclear factor-κB is activated in alveolar macrophages from patients with acute respiratory distress syndrome. Crit Care Med 24: 1285–1292
Donnelly SC, Strieter RM, Kunkel SL et al. (1993) Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet 341: 643–647
Hai T, Curran T (1991) Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci USA 88: 1–5
Karin M (1995) The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem 270: 16483–16486
Karin M, Liu Zg, Zandi E (1997) AP-1 function and regulation. Curr Opin Cell Biol 9: 240–246
Adcock IM, Shirasaki H, Gelder CM, Peters MJ, Brown CR, Barnes PJ (1994) The effects of glucocorticoids on phorbol ester and cytokine stimulated transcription factor activation in human lung. Life Sci 55: 1147–1153
Kyriakis JM, Bangrjee P, Nikolakaki E et al. (1994) The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369: 156–160
Westwick JK, Weitzel C, Minden A, Karin M, Brenner DA (1994) Tumor necrosis factor alpha stimulates AP-1 activity through prolonged activation of the c-Jun kinase. J Biol Chem 269: 26396–26401
Camhi SL, Alam J, Otterbein L, Sylvester SL, Choi AM (1995) Induction of heme oxygenase-1 gene expression by lipopolysaccharide is mediated by AP-1 activation. Am J Respir Cell Mol Biol 13: 387–398
Demoly P, Basset-Seguin N, Chanez P et al. (1992) c-Fos proto-oncogene expression in bronchial biopsies of asthmatics. Am J Respir Cell Mol Biol 7: 128–133
Ponta H, Cato ACB, Herrlick P (1992) Interference of specific transcription factors. Biochim Biophys Acta 1129: 255–261
Kishimoto T, Taga T, Akira S (1994) Cytokine signal transduction. Cell 76: 253–262
Gosset P, Tsicopoulos A, Wallaert B, Vannimenus C, Joseph M, Tonnel AB, Capron A (1991) Increased secretion by tumor necrosis factor α and interleukin 6 by alveolar macrophages consecutive to the development of the late asthmatic reaction. J Allergy Clin Immunol 88: 561–571
Gosset P, Tsicopoulos A, Wallaert B, Vannimenus C, Joseph M, Tonnel AB, Capron A (1992) Tumor necrosis factor α and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation. Am Rev Respir Dis 146: 768–774
Grunberg K, Smits HH, Timers MC et al. (1997) Experimental rhinovirus 16 infection. Effects on cell differentials and soluble markers in sputum in asthmatic subjects. Am J Respir Crit Care Med 156: 609–616
Darnell JE, Kerr IM, Stark GR (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signalling proteins. Science 264: 1415–1421
Ihle JN, Witthuhn BA, Quelle FW, Yamamoto K, Thienfeloer WC, Kreider B, Silvennoinev O (1994) Signalling by the cytokine receptor superfamily: JAKs and STATs. Trends Biochem Sci 19: 222–225
Battacharya S, Eckner R, Grossman S, Oldread E, Arany Z, D’Andrea A, Livingston DM (1996) Cooperation of Stat 2 and p300/CBP in signaling induced by interferon-alpha. Nature 383: 344–347
Zhang JJ, Vinkemeier U, Gu W, Chakravarti D, Horvath CM, Darnell JE (1996) Two contact regions between STAT1 and CBP/p300 in interferon-γ signalling. Proc Natl Acad Sci USA 93: 15092–15096
Hou J, Schindler U, Henzel WJ, Ho TC, Brasseur M, McKnight SL (1994) An interleukin-4-induced transcription factor: IL-4 stat. Science 265: 1701–1706
Takeda K, Tanaka T, Shi W et al. (1996) Essential role for Stat6 in IL-4 signaling. Nature 380: 627–630
Kaplan MH, Schindler U, Smiley ST, Grusby MJ (1996) Stat6 is required for mediating responses to IL-4 and for the development of Th2 cells. Immunity 4: 313–319
Bacon CM, Petricoin EF, Ortaldo JR, Rees SC, Larner AC, Johnston JA, O’Shea JJ (1995) IL-12 induces tyrosine phosphorylation and activation of STAT-4 in human lymphocytes. Proc Natl Acad Sci USA 92: 7303–7311
Kaplan MH, Sun Y, Hoey T, Grusby MJ (1996) Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 382: 174–177
Pazdrak K, Stafford S, Alam R (1995) The activation of the Jak-STAT 1 signalling pathway by IL-5 in eosinophils. J Immunol 155: 397–402
van der Bruggen T, Caldenhoven E, Kanters D, Coffer P, Raaijmakers JA, Lammers JW, Koenderman L (1995) Interleukin-5 signaling in human eosinophils involves JAK2 tyrosine kinase and Stat1α. Blood 85: 1442–1448
Mui ALF, Wakao H, O’Farrell AM, Miyajima A (1995) Interleukin-3, granulocyte-macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs. EMBO J 14: 1166–1175
Naka T, Narazaki M, Hirata M et al. (1997) Structure and function of a new STAT-induced STAT inhibitor. Nature 387: 924–929
Starr R, Willson TA, Viney EM et al. (1997) A family of cytokine-inducible inhibitors of signalling. Nature 387: 917–921
Yamamoto KK, Gonzalez GA, Biggs WH, Montminy MR (1988) Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Nature 334: 494–498
Chrivia JC, Kwok RPS, Lamb N, Hagiwara M, Montminy MR, Goodman RH (1993) Phosphorylated CREB specifically binds to the nuclear factor CBP. Nature 365: 855–859
Collins S, Altschmied J, Herbsman O, Caron MG, Mellon PL, Lefkowitz RJ (1990) A cAMP element in the β2-adrenerigc receptor gene confers autoregulation by cAMP. J Biol Chem 265: 19930–19935
Peters MJ, Adcock IM, Brown CR, Barnes PJ (1995) β-Adrenoceptor agonists interfere with glucocorticoid receptor DNA binding in rat lung. Eur J Pharmacol (Mol Pharmacol Section) 289: 275–281
Nishikawa M, Mak JCW, Shirasaki H, Barnes PJ (1993) Differential down-regulation of pulmonary β1-and β2-adrenoceptor messenger RNA with prolonged in vivo infusion of isoprenaline. Eur J Pharmacol (Mol Section) 247: 131–138
Mak JCW, Nishikawa M, Shirasaki H, Miyayasu K, Barnes PJ (1995) Protective effects of a glucocorticoid on down-regulation of pulmonary β2-adrenergic receptors in vivo. J Clin Invest 96: 99–106
Masquilier D, Sassone-Corsi P (1992) Transcriptional cross talk: nuclear factors CREM and CREB bind to AP-1 sites and inhibit activation by Jun. J Biol Chem 267: 22460–22466
Imai F, Minger JN, Mitchell JA, Yamamoto KR, Granner DK (1993) Glucocorticoid receptor — cAMP response element-binding protein interaction and the response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids. J Biol Chem 268: 5353–5356
Stevens DA, Barnes PJ, Adcock IM (1995) β-Agonists inhibit DNA binding of glucocorticoid receptors in human pulmonary and bronchial epithelial cells. Am J Resp Crit Care Med 151:A195
Adcock IM, Stevens DA, Barnes PJ (1996) Interactions between steroids and β2-agonists. Eur Respir J 9: 160–168
Janknecht R, Hunter T (1996) A growing coactivator network Nature 383: 22–23
Arias J, Alberts AS, Brindle P et al. (1994) Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature 370: 226–229
Kamei Y, Xu L, Heinzel T et al. (1996) A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 85: 403–414
Perkins ND, Felzien LK, Betts JC, Leung K, Beach DH, Nabel GJ (1997) Regulation of NF-κB by cyclin-dependent kinases associated with the p300 coactivator. Science 275: 523–526
Smith CL, Onate SA, Tsai MJ, O’Malley BW (1996) CREB binding protein acts synergistically with steroid receptor coactivator-1 to enhance steroid receptor-dependent transcription. Proc Natl Acad Sci USA 93: 8884–8888
Yao PM, Buhler JM, D’Ortho MP, Lebargy F, Delclaux C, Harf A, Lafuma C (1996) Expression of matrix metalloproteinase gelatinases A and B by cultured epithelial cells from human bronchial explants. J Biol Chem 271: 15580–15589
Hong H, Kohli K, Garabedian MJ, Stallcup MR (1997) GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors. Mol Cell Biol 17: 2735–2744
Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK, Rosenfeld MG (1997) The transcriptional co-activator p/CIP binds CBP and mediates nuclear receptor function. Nature 387: 677–684
Heery DM, Kalkhoven E, Hoare S, Parker MG (1997) A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature 387: 733–736
Ogryzko VV, Schlitz RL, Russanova V, Howard BH, Nakatani Y (1996) The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87: 953–959
Wolffe AP (1997) Sinful repression. Nature 387: 16–17
Nagy L, Kao HY, Chakravarti D et al. (1997) Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell 89: 373–380
Heinzel T, Lavinsky RM, Mullen TM et al. (1997) A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature 387: 43–48
Beato M, Herrlich P, Schutz G (1995) Steroid hormone receptors: many actors in search of aplot. Cell 83: 851–857
Adcock IM, Gilbey T, Gelder CM, Chung KF, Barnes PJ (1996) Glucocorticoid receptor localization in normal human lung and asthmatic lung. Am J Respir Crit Care Med 154: 771–782
Truss M, Beato M (1993) Steroid hormone receptors: interaction with deoxyribonucleic acid and transcription factors. Endocr Rev 14: 459–479
Mak JCW, Grandordy B, Barnes PJ (1994) High affinity [3H]formoterol binding sites in lung: characterization and autoradiographic mapping. Eur J Pharmacol (Mol Section) 269: 35–41
Barnes PJ (1996) Mechanism of action of glucocorticoids in asthma. Am J Respir Crit Care Med 154: S21–S27
Scheinman RI, Cogswell PC, Lofquist AK, Baldwin AS (1995) Role of transcriptional activation of IκB-α in mediating immunosuppression by glucocorticoids. Science 270: 283–286
Brostjan C, Anrather J, Csizmadia V, Stoka D, Soares M, Bach FH, Winkler H (1996) Glucocorticoid-mediated repression of NF-κB activity in endothelial cells does not involve induction of I κB α synthesis. J Biol Chem 271: 19612–19616
Newton R, Hart LA, Adcock IM, Barnes PJ (1997) Effect of glucocorticoids on IL-1β-induced NF-κB binding and expression in type II alveolar cells — no evidence for down-regulation by IκB. Am J Respir Crit Care Med 155: A699
Heck S, Bender K, Kullmann M, Gottlicher M, Herrlich P, Cato AC (1997) IκBα-independent downregulation of NF-κB activity by glucocorticoid receptor. EMBO J 16: 4698–4707
Barnes PJ, Adcock IM (1993) Anti-inflammatory actions of steroids: molecular mechanisms. Trends Pharmacol Sci 14: 436–441
Ray A, Prefontaine KE (1994) Physical association and functional antagonism between the p65 subunit of transcription factor NF-κB and the glucocorticoid receptor. Proc Natl Acad Sci USA 91: 752–756
Caldenhoven E, Liden J, Wissink S et al. (1995) Negative cross-talk between RelA and the glucocorticoid receptor: a possible mechanism for the antiinflammatory action of glucocorticoids. Mol Endocrinol 9: 401–412
Stocklin E, Wisler M, Gouilleux F, Groner B (1996) Functional interactions between Stat5 and the glucocorticoid receptor. Nature 383: 726–728
Kleinert H, Euchenhofer C, Ihrig Biedert I, Forstermann U (1996) Glucocorticoids inhibit the induction of nitric oxide synthase II by down-regulating cytokine-induced activity of transcription factor nuclear factor-kappa B. Mol Pharmacol 49: 15–21
Giaid A, Saleh D, Lim S, Barnes PJ, Ernst P (1998) Formation of peroxynitrite in asthmatic airways. Am J Respir Crit Care Med 157: A870
Kharitonov SA, Yates D, Barnes PJ (1995) Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections. Eur Respir J 8: 295–297
Kwon OJ, Jose PJ, Robbins RA, Schall TJ, Williams TJ, Barnes PJ (1995) Glucocorticoids inhibition of RANTES expression in human lung epithelial cells. Am J Respir Cell Mol Med 12: 488–496
Berkman N, Robichaud A, Krishnan VL, Barnes PJ, Chung KF (1996) Expression of RANTES in human airway epithelial cells: effect of corticosteroids and interleukins-4, 10 and 13. Immunology 87: 599–603
Wang H, Devalia JL, Xia C, Sapsford RJ, Davies RJ (1996) Expression of RANTES by human bronchial epithelial cells in vitro and in vivo and the effect of corticosteroids. Am J Respir Cell Mol Biol 14: 27–35
Barnes PJ, Adcock IM (1995) Steroid-resistant asthma. Q J Med 88: 455–468
Barnes PJ, Greening AP, Crompton GK (1995) Glucocorticoid resistance in asthma. Am J Respir Crit Care Med 152: 125S–140S
Szefler SJ, Leung DY (1997) Glucocorticoid-resistant asthma: pathogenesis and clinical implications for management. Eur Respir J 10: 1640–1647
Adcock IM, Lane SJ, Brown CA, Peters MJ, Lee TH, Barnes PJ (1995) Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma. J Immunol 154: 3000–3005
Adcock IM, Lane SJ, Brown CA, Lee TH, Barnes PJ (1995) Abnormal glucocorticoid receptor/AP-1 interaction in steroid resistant asthma. J Exp Med 182: 1951–1958
Adcock IM, Lane SJ, Barnes PJ, Lee TH (1996) Enhanced phorbol ester-induced c-Fos transcription and translation in steroid-resistant asthma. Am J Respir Crit Care Med 153: A682
Adcock IM, Brady H, Lim S, Karin M, Barnes PJ (1997) Increased JUN kinase activity in peripheral blood monocytes from steroid-resistant asthmatic subjects. Am J Respir Crit Care Med 155: A288
Lane SJ, Atkinson BA, Swimanathan R, Lee TH (1996) Hypothalamic—pituitary axis in corticosteroid-resistant asthma. Am J Respir Crit Care Med 153: 1510–1514
Shibasaki F, Price ER, Milan D, McKeon F (1996) Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4. Nature 382: 370–373
Hoey T, Sun YL, Williamson K, Yu X (1995) Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins. Immunity 2: 461–472
Jain J, McCaffrey PG, Valge Archer VE, Rao A (1992) Nuclear factor of activated T cells contains Fos and Jun. Nature 356: 801–804
Northrop JP, Ullman KS, Crabtree GR (1993) Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells (NF-AT). J Biol Chem 268: 2917–2923
Palmer JBD, Cuss FMC, Mulderry PK et al. (1987) Calcitonin gene-related peptide is localized to human airway nerves and potently constricts human airway smooth muscle. Br J Pharmacol 91: 95–101
Wright LC, Cammisuli S, Baboulene L, Fozzard J, Adcock IM, Barnes PJ (1995) Cyclosporin A and glucocorticoids interact synergistically in T lymphocytes: implications for asthma therapy. Am J Resp Crit Care Med 151: A675
Lee HJ, Matsuda I, Naito Y, Yokota T, Arai N, Arai K (1994) Signals and nuclear factors that regulate the expression of interleukin-4 and interleukin-5 genes in helper T cells. J Allergy Clin Immunol 94: 594–604
Hodge MR, Rooney JW, Glimcher LH (1995) The proximal promoter of the IL-4 gene is composed of multiple essential regulatory sites that bind at least two distinct factors. J Immunol 154: 6397–6405
Hodge MR, Ranger AM, Charles de la Brousse F, Hoey T, Grusby MJ, Glimcher LH (1996) Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Immunity 4: 397–405
Hodge MR, Chun HJ, Rengarajan J, Alt A, Lieberson R, Glimcher LH (1996) NF-AT-driven interleukin-4 transcription potentiated by NIP45. Science 274: 1903–1905
Lee HJ, Masuda ES, Arai N, Arai K, Yokota T (1995) Definition of cis-regulatory elements of the mouse interleukin-5 gene promoter. Involvement of nuclear factor of activated T cell-related factors in interleukin-5 expression. J Biol Chem 270: 17541–17550
Prieschl EE, Gouilleux Gruart V, Walker C, Harrer NE, Baumruker T (1995) A nuclear factor of activated T cell-like transcription factor in mast cells is involved in IL-5 gene regulation after IgE plus antigen stimulation. J Immunol 154: 6112–6119
Mori A, Kaminuma O, Suko M et al. (1997) Two distinct pathways of interleukin-5 synthesis in allergen-specific human T cell clones are suppressed by glucocorticoids. Blood 89: 2891–2900
Manning AM (1996) Transcription factors: a new frontier in drug discovery. Drug Devel Ther 1: 151–160
Heck S, Kullmann M, Grast A, Ponta H, Rahmsdorf HJ, Herrlich P, Cato ACB (1994) A distinct modulating domain in glucocorticoid receptor monomers in the repression of activity of the transcription factor AP-1. EMBO J 13: 4087–4095
Adcock IM, Barnes PJ (1996) Ligand-induced differentiation of glucocorticoid receptor (GR) transrepression and transactivation. Am J Respir Crit Care Med 153: A243
Vayssière BM, Dupont S, Choquart A et al. (1997) Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepresson exhibit antiinflammatory activity in vivo. Mol Endocrinol 11: 1245–1255
Barnes PJ, Adcock IM (1997) NF-κB: a pivotal role in asthma and a new target for therapy. Trends Pharmacol Sci 18: 46–50
Miyajima T, Kotake Y (1995) Spin trapping agent, phenyl N-tert-butyl nitrone, inhibits induction of nitric oxide synthase in endotoxin-induced shock in mice. Biochem Biophys Res Commun 215: 114–121
Pahl HL, Krauss B, Schultze-Osthoff K et al. (1996) The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-κB. J Exp Med 183: 1829–1840
Wang P, Wu P, Siegel MI, Egan RW, Billah MM (1995) Interleukin(IL)-10 inhibits nuclear factor kappa B activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. J Biol Chem 270: 9558–9563
John M, Lim S, Seybold J, Robichaud A, O’Connor B, Barnes PJ, Chung KF (1997) Inhaled corticosteroids increase IL-10 but reduce MIP-1α, GM-CSF and IFN-γ release from alveolar macrophages in asthma. Am J Respir Crit Care Med
Yaron A, Gonen H, Alkalay I et al. (1997) Inhibition of NF-κB cellular function via specific targeting of the IκB-ubiquitin ligase. EMBO J 16: 6486–6494
Wrighton CJ, Hofer-Warbinek R, Moll T, Eytner R, Bach FH, de Martin R (1996) Inhibition of endothelial cell activation by adenovirus-mediated expression of IκB-α, an inhibitor of transcription factor NF-κB. J Exp Med 183: 1013–1022
Wallace J, Adcock IM, Barnes PJ (1996) Retinoic acid potentiates the inhibitory effects of dexamethasone on AP-1 DNA binding in epithelial cells. Am J Respir Crit Care Med 153: A209
Rowe A (1997) Retinoid X receptors. Int J Biochem Cell Biol 29: 275–278
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Basel AG
About this chapter
Cite this chapter
Barnes, P.J., Adcock, I.M. (1999). Transcription Factors and Inflammatory Lung Disease. In: Stockley, R.A. (eds) Molecular Biology of the Lung. Respiratory Pharmacology and Pharmacotherapy. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8784-7_3
Download citation
DOI: https://doi.org/10.1007/978-3-0348-8784-7_3
Publisher Name: Birkhäuser, Basel
Print ISBN: 978-3-0348-9773-0
Online ISBN: 978-3-0348-8784-7
eBook Packages: Springer Book Archive