| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B and STAT6 in Human Airway Epithelial Cells1
Division of Clinical Immunology and Allergy, Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224
The C-C chemokine eotaxin is a potent chemoattractant for
eosinophils and probably plays an important role in the pathogenesis of
asthma, although the mechanisms of its regulation are not well known.
Airway epithelial cells express eotaxin mRNA and protein after
stimulation with a variety of cytokines. We focused on the molecular
mechanisms of eotaxin gene regulation by TNF-
and IL-4 in the airway
epithelial cell line, BEAS-2B. Cells were transfected with luciferase
reporter plasmids, which contained up to 1363 bp of the eotaxin
promoter. Eotaxin promoter activity was increased by TNF- (2.5-fold)
and IL-4 (1.5-fold), respectively. The combination of TNF- and IL-4
produced 3.6-fold activation of the eotaxin promoter. The eotaxin
promoter contains overlapping consensus binding sites for transcription
factors, NF-
B and STAT6, which are known to mediate responses to
TNF- and IL-4, respectively. Electrophoretic mobility shift assays
revealed NF-B binding after TNF- stimulation and STAT6 binding
after IL-4 stimulation using a DNA probe derived from the eotaxin
promoter. Mutant plasmids were generated to define the roles of these
transcription factors in eotaxin promoter activity. TNF-
stimulation, but not IL-4 stimulation, was lost in plasmids mutated at
the NF-B binding site, whereas IL-4 stimulation, but not TNF-
stimulation, was lost in plasmids mutated at the STAT6 binding site.
When both sites were mutated, all transcriptional activation was lost.
These results imply that TNF- and IL-4 stimulate expression of the
eotaxin gene by activating NF-B and STAT6.
This article has been cited by other articles:
|
|
 |
|
  A. Rodrigues, D. B.C. Queiroz, L. Honda, E. J. R. Silva, S. H. Hall, and M. C. W. Avellar Activation of Toll-Like Receptor 4 (TLR4) by In Vivo and In Vitro Exposure of Rat Epididymis to Lipopolysaccharide from Escherichia Coli Biol Reprod, December 1, 2008; 79(6): 1135 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ahrens, A. Waddell, L. Seidu, C. Blanchard, R. Carey, E. Forbes, M. Lampinen, T. Wilson, E. Cohen, K. Stringer, et al. Intestinal Macrophage/Epithelial Cell-Derived CCL11/Eotaxin-1 Mediates Eosinophil Recruitment and Function in Pediatric Ulcerative Colitis J. Immunol., November 15, 2008; 181(10): 7390 - 7399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Hudson, G. P. Christophi, R. C. Gruber, J. R. Wilmore, D. A. Lawrence, and P. T. Massa Induction of IL-33 expression and activity in central nervous system glia J. Leukoc. Biol., September 1, 2008; 84(3): 631 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nonaka, N. Ogihara, A. Fukumoto, A. Sakanushi, R. Pawankar, and T. Yagi Combined Stimulation of Nasal Polyp Fibroblasts With Poly IC, Interleukin 4, and Tumor Necrosis Factor {alpha} Potently Induces Production of Thymus- and Activation-Regulated Chemokine Arch Otolaryngol Head Neck Surg, June 1, 2008; 134(6): 630 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kato, S. Favoreto Jr., P. C. Avila, and R. P. Schleimer TLR3- and Th2 Cytokine-Dependent Production of Thymic Stromal Lymphopoietin in Human Airway Epithelial Cells J. Immunol., July 15, 2007; 179(2): 1080 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Novak, A. Muller, N. Harrer, C. Gunther, J. M. Carballido, and M. Woisetschlager CCL23 Expression Is Induced by IL-4 in a STAT6-Dependent Fashion J. Immunol., April 1, 2007; 178(7): 4335 - 4341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Dorscheid, B. J. Patchell, O. Estrada, B. Marroquin, R. Tse, and S. R. White Effects of corticosteroid-induced apoptosis on airway epithelial wound closure in vitro Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L794 - L801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Miyazaki, T. Satoh, K. Nishioka, and H. Yokozeki STAT-6-Mediated Control of P-Selectin by Substance P and Interleukin-4 in Human Dermal Endothelial Cells Am. J. Pathol., August 1, 2006; 169(2): 697 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Fritz, C. Kerr, L. Tong, D. Smyth, and C. D. Richards Oncostatin-M Up-Regulates VCAM-1 and Synergizes with IL-4 in Eotaxin Expression: Involvement of STAT6 J. Immunol., April 1, 2006; 176(7): 4352 - 4360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Broide, T. Lawrence, T. Doherty, J. Y. Cho, M. Miller, K. McElwain, S. McElwain, and M. Karin Allergen-induced peribronchial fibrosis and mucus production mediated by I{kappa}B kinase {beta}-dependent genes in airway epithelium PNAS, December 6, 2005; 102(49): 17723 - 17728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lehtonen, V. Veckman, T. Nikula, R. Lahesmaa, L. Kinnunen, S. Matikainen, and I. Julkunen Differential Expression of IFN Regulatory Factor 4 Gene in Human Monocyte-Derived Dendritic Cells and Macrophages J. Immunol., November 15, 2005; 175(10): 6570 - 6579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Fan, N. M. Heller, M. Gorospe, U. Atasoy, and C. Stellato The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy Eur. Respir. J., November 1, 2005; 26(5): 933 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Minamoto, H. Harada, V. N. Lama, M. A. Fedarau, and D. J. Pinsky Reciprocal regulation of airway rejection by the inducible gas-forming enzymes heme oxygenase and nitric oxide synthase J. Exp. Med., July 18, 2005; 202(2): 283 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nie, A. J. Knox, and L. Pang {beta}2-Adrenoceptor Agonists, Like Glucocorticoids, Repress Eotaxin Gene Transcription by Selective Inhibition of Histone H4 Acetylation J. Immunol., July 1, 2005; 175(1): 478 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Pope, P. C. Fulkerson, C. Blanchard, H. S. Akei, N. M. Nikolaidis, N. Zimmermann, J. D. Molkentin, and M. E. Rothenberg Identification of a Cooperative Mechanism Involving Interleukin-13 and Eotaxin-2 in Experimental Allergic Lung Inflammation J. Biol. Chem., April 8, 2005; 280(14): 13952 - 13961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Chang, J. S. Kim, J. H. Lee, J. I. Cho, T. Y. Rhim, S.-T. Uh, B. L. Park, I. Y. Chung, C.-S. Park, and H. D. Shin A Single Nucleotide Polymorphism on the Promoter of eotaxin1 Associates with Its mRNA Expression and Asthma Phenotypes J. Immunol., February 1, 2005; 174(3): 1525 - 1531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nie, L. Corbett, A. J. Knox, and L. Pang Differential Regulation of Chemokine Expression by Peroxisome Proliferator-activated Receptor {gamma} Agonists: INTERACTIONS WITH GLUCOCORTICOIDS AND {beta}2-AGONISTS J. Biol. Chem., January 28, 2005; 280(4): 2550 - 2561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Stellato Post-transcriptional and Nongenomic Effects of Glucocorticoids Proceedings of the ATS, November 1, 2004; 1(3): 255 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Heller, S. Matsukura, S. N. Georas, M. R. Boothby, P. B. Rothman, C. Stellato, and R. P. Schleimer Interferon-{gamma} Inhibits STAT6 Signal Transduction and Gene Expression in Human Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 573 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Desmet, P. Gosset, B. Pajak, D. Cataldo, M. Bentires-Alj, P. Lekeux, and F. Bureau Selective Blockade of NF-{kappa}B Activity in Airway Immune Cells Inhibits the Effector Phase of Experimental Asthma J. Immunol., November 1, 2004; 173(9): 5766 - 5775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hoshino, T. Tsuji, J. Matsuzaki, T. Jinushi, S. Ashino, T. Teramura, K. Chamoto, Y. Tanaka, Y. Asakura, T. Sakurai, et al. STAT6-mediated signaling in Th2-dependent allergic asthma: critical role for the development of eosinophilia, airway hyper-responsiveness and mucus hypersecretion, distinct from its role in Th2 differentiation Int. Immunol., October 1, 2004; 16(10): 1497 - 1505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takamura, Y. Nasuhara, M. Kobayashi, T. Betsuyaku, Y. Tanino, I. Kinoshita, E. Yamaguchi, S. Matsukura, R. P. Schleimer, and M. Nishimura Retinoic acid inhibits interleukin-4-induced eotaxin production in a human bronchial epithelial cell line Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L777 - L785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Peng, T. Matsuda, and S. J. Hirst Signaling Pathways Regulating Interleukin-13-stimulated Chemokine Release from Airway Smooth Muscle Am. J. Respir. Crit. Care Med., March 1, 2004; 169(5): 596 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Atasoy, S. L. Curry, I. Lopez de Silanes, A.-B. Shyu, V. Casolaro, M. Gorospe, and C. Stellato Regulation of Eotaxin Gene Expression by TNF-{alpha} and IL-4 Through mRNA Stabilization: Involvement of the RNA-Binding Protein HuR J. Immunol., October 15, 2003; 171(8): 4369 - 4378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Chen, R. Lund, T. Aittokallio, M. Kosonen, O. Nevalainen, and R. Lahesmaa Identification of Novel IL-4/Stat6-Regulated Genes in T Lymphocytes J. Immunol., October 1, 2003; 171(7): 3627 - 3635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Faffe, T. Whitehead, P. E. Moore, S. Baraldo, L. Flynt, K. Bourgeois, R. A. Panettieri, and S. A. Shore IL-13 and IL-4 promote TARC release in human airway smooth muscle cells: role of IL-4 receptor genotype Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L907 - L914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Richter, A. M. Cantin, C. Beaulieu, A. Cloutier, and P. Larivee Zinc chelators inhibit eotaxin, RANTES, and MCP-1 production in stimulated human airway epithelium and fibroblasts Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L719 - L729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Honda, M. Arima, G. Cheng, S. Taki, H. Hirata, F. Eda, F. Fukushima, B. Yamaguchi, M. Hatano, T. Tokuhisa, et al. Prostaglandin D2 Reinforces Th2 Type Inflammatory Responses of Airways to Low-dose Antigen through Bronchial Expression of Macrophage-derived Chemokine J. Exp. Med., August 18, 2003; 198(4): 533 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Takizawa, S. Abe, H. Okazaki, T. Kohyama, I. Sugawara, Y. Saito, T. Ohtoshi, S. Kawasaki, M. Desaki, K. Nakahara, et al. Diesel exhaust particles upregulate eotaxin gene expression in human bronchial epithelial cells via nuclear factor-kappa B-dependent pathway Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L1055 - L1062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Chibana, Y. Ishii, T. Asakura, and T. Fukuda Up-Regulation of Cysteinyl Leukotriene 1 Receptor by IL-13 Enables Human Lung Fibroblasts to Respond to Leukotriene C4 and Produce Eotaxin J. Immunol., April 15, 2003; 170(8): 4290 - 4295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Stutz, L. A. Pickart, A. Trifilieff, T. Baumruker, E. Prieschl-Strassmayr, and M. Woisetschlager The Th2 Cell Cytokines IL-4 and IL-13 Regulate Found in Inflammatory Zone 1/Resistin-Like Molecule {alpha} Gene Expression by a STAT6 and CCAAT/Enhancer-Binding Protein-Dependent Mechanism J. Immunol., February 15, 2003; 170(4): 1789 - 1796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Mattes, M. Hulett, W. Xie, S. Hogan, M. E. Rothenberg, P. Foster, and C. Parish Immunotherapy of Cytotoxic T Cell-resistant Tumors by T Helper 2 Cells: An Eotaxin and STAT6-dependent Process J. Exp. Med., February 3, 2003; 197(3): 387 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Langdon, C. Kerr, L. Tong, and C. D. Richards Oncostatin M Regulates Eotaxin Expression in Fibroblasts and Eosinophilic Inflammation in C57BL/6 Mice J. Immunol., January 1, 2003; 170(1): 548 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-w. Jeong, M.-H. Yoo, T. S. Kim, J.-H. Kim, and I. Y. Kim Protection of Mice from Allergen-induced Asthma by Selenite. PREVENTION OF EOSINOPHIL INFILTRATION BY INHIBITION OF NF-kappa B ACTIVATION J. Biol. Chem., May 10, 2002; 277(20): 17871 - 17876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Hirst, M. P. Hallsworth, Q. Peng, and T. H. Lee Selective Induction of Eotaxin Release by Interleukin-13 or Interleukin-4 in Human Airway Smooth Muscle Cells Is Synergistic with Interleukin-1beta and Is Mediated by the Interleukin-4 Receptor alpha -Chain Am. J. Respir. Crit. Care Med., April 15, 2002; 165(8): 1161 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Georas, L. A. Beck, and C. Stellato What Is Eotaxin Doing in the Pleura? . Insights into Innate Immunity from Pleural Mesothelial Cells Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 384 - 387. [Full Text] [PDF]
|
|
|
|
|
|
M. E. Poynter, C. G. Irvin, and Y. M. W. Janssen-Heininger Rapid Activation of Nuclear Factor-{kappa}B in Airway Epithelium in a Murine Model of Allergic Airway Inflammation Am. J. Pathol., April 1, 2002; 160(4): 1325 - 1334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Relloso, A. Puig-Kroger, O. M. Pello, J. L. Rodriguez-Fernandez, G. de la Rosa, N. Longo, J. Navarro, M. A. Munoz-Fernandez, P. Sanchez-Mateos, and A. L. Corbi DC-SIGN (CD209) Expression Is IL-4 Dependent and Is Negatively Regulated by IFN, TGF-{beta}, and Anti-Inflammatory Agents J. Immunol., March 15, 2002; 168(6): 2634 - 2643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Blease, J. M. Schuh, C. Jakubzick, N. W. Lukacs, S. L. Kunkel, B. H. Joshi, R. K. Puri, M. H. Kaplan, and C. M. Hogaboam Stat6-Deficient Mice Develop Airway Hyperresponsiveness and Peribronchial Fibrosis during Chronic Fungal Asthma Am. J. Pathol., February 1, 2002; 160(2): 481 - 490. [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]
|
|
|
|
 |
|
 K. Fukuda, Y. Fujitsu, N. Kumagai, and T. Nishida Characterization of the Interleukin-4 Receptor Complex in Human Corneal Fibroblasts Invest. Ophthalmol. Vis. Sci., January 1, 2002; 43(1): 183 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nakamura, A. D. Luster, H. Tateno, S. Jedrzkiewicz, G. Tamura, K. J. Haley, E. A. Garcia-Zepeda, K. Yamaguchi, and C. M. Lilly IL-4 differentially regulates eotaxin and MCP-4 in lung epithelium and circulating mononuclear cells Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1288 - L1302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fujiie, K. Hieshima, D. Izawa, T. Nakayama, R. Fujisawa, H. Ohyanagi, and O. Yoshie Proinflammatory cytokines induce liver and activation-regulated chemokine/macrophage inflammatory protein-3{alpha}/CCL20 in mucosal epithelial cells through NF-{kappa}B Int. Immunol., October 1, 2001; 13(10): 1255 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hoeck and M. Woisetschlager Activation of Eotaxin-3/CCL26 Gene Expression in Human Dermal Fibroblasts Is Mediated by STAT6 J. Immunol., September 15, 2001; 167(6): 3216 - 3222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Mattes, M. Yang, A. Siqueira, K. Clark, J. MacKenzie, A. N. J. McKenzie, D. C. Webb, K. I. Matthaei, and P. S. Foster IL-13 Induces Airways Hyperreactivity Independently of the IL-4R{alpha} Chain in the Allergic Lung J. Immunol., August 1, 2001; 167(3): 1683 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Afanasyeva, Y. Wang, Z. Kaya, S. Park, M. J. Zilliox, B. H. Schofield, S. L. Hill, and N. R. Rose Experimental Autoimmune Myocarditis in A/J mice Is an Interleukin-4-Dependent Disease with a Th2 Phenotype Am. J. Pathol., July 1, 2001; 159(1): 193 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Matsukura, C. Stellato, S. N. Georas, V. Casolaro, J. R. Plitt, K. Miura, S. Kurosawa, U. Schindler, and R. P. Schleimer Interleukin-13 Upregulates Eotaxin Expression in Airway Epithelial Cells by a STAT6-Dependent Mechanism Am. J. Respir. Cell Mol. Biol., June 1, 2001; 24(6): 755 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mathew, J. A. MacLean, E. DeHaan, A. M. Tager, F. H.Y. Green, and A. D. Luster Signal Transducer and Activator of Transcription 6 Controls Chemokine Production and T Helper Cell Type 2 Cell Trafficking in Allergic Pulmonary Inflammation J. Exp. Med., May 7, 2001; 193(9): 1087 - 1096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hoeck and M. Woisetschlager STAT6 Mediates Eotaxin-1 Expression in IL-4 or TNF-{{alpha}}-Induced Fibroblasts J. Immunol., April 1, 2001; 166(7): 4507 - 4515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jedrzkiewicz, H. Nakamura, E. S. Silverman, A. D. Luster, N. Mansharamani, K. H. In, G. Tamura, and C. M. Lilly IL-1beta induces eotaxin gene transcription in A549 airway epithelial cells through NF-kappa B Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1058 - L1065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Ehret, P. Reichenbach, U. Schindler, C. M. Horvath, S. Fritz, M. Nabholz, and P. Bucher DNA Binding Specificity of Different STAT Proteins. COMPARISON OF IN VITRO SPECIFICITY WITH NATURAL TARGET SITES J. Biol. Chem., February 23, 2001; 276(9): 6675 - 6688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Harrington and A. Sharma Transcription Factors Recognizing Overlapping C1-A2 Binding Sites Positively Regulate Insulin Gene Expression J. Biol. Chem., January 5, 2001; 276(1): 104 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Stutz, J. Hoeck, F. Natt, B. Cuenoud, and M. Woisetschlager Inhibition of Interleukin-4- and CD40-induced IgE Germline Gene Promoter Activity by 2'-Aminoethoxy-modified Triplex-forming Oligonucleotides J. Biol. Chem., April 6, 2001; 276(15): 11759 - 11765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Huber, A. Denk, R. U. Peter, L. Weber, N. Kraut, and T. Wirth The IKK-2/Ikappa Balpha /NF-kappa B Pathway Plays a Key Role in the Regulation of CCR3 and eotaxin-1 in Fibroblasts. A CRITICAL LINK TO DERMATITIS IN Ikappa Balpha -DEFICIENT MICE J. Biol. Chem., January 4, 2002; 277(2): 1268 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Moore, T. L. Church, D. D. Chism, R. A. Panettieri Jr., and S. A. Shore IL-13 and IL-4 cause eotaxin release in human airway smooth muscle cells: a role for ERK Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L847 - L853. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
