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*
Department of Immunology IMM-25, Scripps Research Institute, La Jolla, CA 92037; and
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
Airway inflammation associated with asthma is characterized by
massive infiltration of eosinophils, mediated in part by specific
chemoattractant factors produced in the lung. Allergen-specific Th2
cells appear to play a central role in asthma; for example, adoptively
transferred Th2 cells induced lung eosinophilia associated with
induction of specific chemokines. Interestingly, Th2 supernatant alone
administered intranasally to naive mice induced eotaxin, RANTES,
monocyte-chemotactic protein-1, and KC expression along with
lung eosinophilia. We tested the major cytokines individually and found
that IL-4 and IL-5 induced higher levels of macrophage-inflammatory
protein-1
and KC; IL-4 also increased the production of
monocyte-chemotactic protein-1; IL-13 and IL-4 induced eotaxin. IL-13
was by far the most potent inducer of eotaxin; indeed, a neutralizing
anti-IL-13 Ab removed most of the eotaxin-inducing activity from
Th2 supernatants, although it did not entirely block the recruitment of
eosinophils. While TNF- did not stimulate eotaxin production by
itself, it markedly augmented eotaxin induction by IL-13. IL-13 was
able to induce eotaxin in the lung of JAK3-deficient mice, suggesting
that JAK3 is not required for IL-13 signaling in airway epithelial
cells; however, eosinophilia was not induced in this situation,
suggesting that JAK3 transduces other IL-13-mediated mechanisms
critical for eosinophil recruitment. Our study suggests that IL-13 is
an important mediator in the pathogenesis of asthma and therefore a
potential target for asthma therapy.
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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]
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N. W. Lukacs, K. K. Tekkanat, A. Berlin, C. M. Hogaboam, A. Miller, H. Evanoff, P. Lincoln, and H. Maassab Respiratory Syncytial Virus Predisposes Mice to Augmented Allergic Airway Responses Via IL-13-Mediated Mechanisms J. Immunol., July 15, 2001; 167(2): 1060 - 1065. [Abstract] [Full Text] [PDF]
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 P.J. Barnes Cytokine modulators as novel therapies for airway disease Eur. Respir. J., July 2, 2001; 18(34_suppl): 67S - 77s. [Abstract] [Full Text] [PDF]
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M. J. Dobrzanski, J. B. Reome, and R. W. Dutton Role of Effector Cell-Derived IL-4, IL-5, and Perforin in Early and Late Stages of Type 2 CD8 Effector Cell-Mediated Tumor Rejection J. Immunol., July 1, 2001; 167(1): 424 - 434. [Abstract] [Full Text] [PDF]
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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]
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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]
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M. Stassen, C. Muller, M. Arnold, L. Hultner, S. Klein-Hessling, C. Neudorfl, T. Reineke, E. Serfling, and E. Schmitt IL-9 and IL-13 Production by Activated Mast Cells Is Strongly Enhanced in the Presence of Lipopolysaccharide: NF-{{kappa}}B Is Decisively Involved in the Expression of IL-9 J. Immunol., April 1, 2001; 166(7): 4391 - 4398. [Abstract] [Full Text] [PDF]
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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]
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S. Kawasaki, H. Takizawa, H. Yoneyama, T. Nakayama, R. Fujisawa, M. Izumizaki, T. Imai, O. Yoshie, I. Homma, K. Yamamoto, et al. Intervention of Thymus and Activation-Regulated Chemokine Attenuates the Development of Allergic Airway Inflammation and Hyperresponsiveness in Mice J. Immunol., February 1, 2001; 166(3): 2055 - 2062. [Abstract] [Full Text] [PDF]
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 F. H. Falcone, H. Haas, and B. F. Gibbs The human basophil: a new appreciation of its role in immune responses Blood, December 15, 2000; 96(13): 4028 - 4038. [Full Text] [PDF]
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N. Zimmermann, S. P. Hogan, A. Mishra, E. B. Brandt, T. R. Bodette, S. M. Pope, F. D. Finkelman, and M. E. Rothenberg Murine Eotaxin-2: A Constitutive Eosinophil Chemokine Induced by Allergen Challenge and IL-4 Overexpression J. Immunol., November 15, 2000; 165(10): 5839 - 5846. [Abstract] [Full Text] [PDF]
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R. Umeshita-Suyama, R. Sugimoto, M. Akaiwa, K. Arima, B. Yu, M. Wada, M. Kuwano, K. Nakajima, N. Hamasaki, and K. Izuhara Characterization of IL-4 and IL-13 signals dependent on the human IL-13 receptor {alpha} chain 1: redundancy of requirement of tyrosine residue for STAT3 activation Int. Immunol., November 1, 2000; 12(11): 1499 - 1509. [Abstract] [Full Text] [PDF]
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J. Deng, V. P. Yeung, D. Tsitoura, R. H. DeKruyff, D. T. Umetsu, and S. Levy Allergen-Induced Airway Hyperreactivity Is Diminished in CD81-Deficient Mice J. Immunol., November 1, 2000; 165(9): 5054 - 5061. [Abstract] [Full Text] [PDF]
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M. Throsby, A. Herbelin, J.-M. Pleau, and M. Dardenne CD11c+ Eosinophils in the Murine Thymus: Developmental Regulation and Recruitment upon MHC Class I-Restricted Thymocyte Deletion J. Immunol., August 15, 2000; 165(4): 1965 - 1975. [Abstract] [Full Text] [PDF]
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S. M. Propst, R. Denson, E. Rothstein, K. Estell, and L. M. Schwiebert Proinflammatory and Th2-Derived Cytokines Modulate CD40-Mediated Expression of Inflammatory Mediators in Airway Epithelia: Implications for the Role of Epithelial CD40 in Airway Inflammation J. Immunol., August 15, 2000; 165(4): 2214 - 2221. [Abstract] [Full Text] [PDF]
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B. LAMKHIOUED, E. A. GARCIA-ZEPEDA, S. ABI-YOUNES, H. NAKAMURA, S. JEDRZKIEWICZ, L. WAGNER, P. M. RENZI, Z. ALLAKHVERDI, C. LILLY, Q. HAMID, et al. Monocyte Chemoattractant Protein (MCP)-4 Expression in the Airways of Patients with Asthma . Induction in Epithelial Cells and Mononuclear Cells by Proinflammatory Cytokines Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 723 - 732. [Abstract] [Full Text] [PDF]
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M. Zaitsu, Y. Hamasaki, M. Matsuo, A. Kukita, K. Tsuji, M. Miyazaki, R. Hayasaki, E. Muro, S. Yamamoto, I. Kobayashi, et al. New induction of leukotriene A4 hydrolase by interleukin-4 and interleukin-13 in human polymorphonuclear leukocytes Blood, July 15, 2000; 96(2): 601 - 609. [Abstract] [Full Text] [PDF]
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D. C. Webb, A. N. J. McKenzie, A. M. L. Koskinen, M. Yang, J. Mattes, and P. S. Foster Integrated Signals Between IL-13, IL-4, and IL-5 Regulate Airways Hyperreactivity J. Immunol., July 1, 2000; 165(1): 108 - 113. [Abstract] [Full Text] [PDF]
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M. J. Dobrzanski, J. B. Reome, and R. W. Dutton Type 1 and Type 2 CD8+ Effector T Cell Subpopulations Promote Long-Term Tumor Immunity and Protection to Progressively Growing Tumor J. Immunol., January 15, 2000; 164(2): 916 - 925. [Abstract] [Full Text] [PDF]
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C. Bandeira-Melo, M. F. Serra, B. L. Diaz, R. S. B. Cordeiro, P. M. R. Silva, H. L. Lenzi, Y. S. Bakhle, C. N. Serhan, and M. A. Martins Cyclooxygenase-2-Derived Prostaglandin E2 and Lipoxin A4 Accelerate Resolution of Allergic Edema in Angiostrongylus costaricensis-Infected Rats: Relationship with Concurrent Eosinophilia J. Immunol., January 15, 2000; 164(2): 1029 - 1036. [Abstract] [Full Text] [PDF]
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S. Ying, Q. Meng, K. Zeibecoglou, D. S. Robinson, A. Macfarlane, M. Humbert, and A. B. Kay Eosinophil Chemotactic Chemokines (Eotaxin, Eotaxin-2, RANTES, Monocyte Chemoattractant Protein-3 (MCP-3), and MCP-4), and C-C Chemokine Receptor 3 Expression in Bronchial Biopsies from Atopic and Nonatopic (Intrinsic) Asthmatics J. Immunol., December 1, 1999; 163(11): 6321 - 6329. [Abstract] [Full Text] [PDF]
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C. Stellato, S. Matsukura, A. Fal, J. White, L. A. Beck, D. Proud, and R. P. Schleimer Differential Regulation of Epithelial-Derived C-C Chemokine Expression by IL-4 and the Glucocorticoid Budesonide J. Immunol., November 15, 1999; 163(10): 5624 - 5632. [Abstract] [Full Text] [PDF]
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I. Sabroe, M. J. Peck, B. J. Van Keulen, A. Jorritsma, G. Simmons, P. R. Clapham, T. J. Williams, and J. E. Pease A Small Molecule Antagonist of Chemokine Receptors CCR1 and CCR3. POTENT INHIBITION OF EOSINOPHIL FUNCTION AND CCR3-MEDIATED HIV-1 ENTRY J. Biol. Chem., August 18, 2000; 275(34): 25985 - 25992. [Abstract] [Full Text] [PDF]
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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]
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