| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Biozentrum, Physiologische Chemie II, Universität Würzburg, Würzburg, Germany;
Klinik und Poliklinik für Haut- und Geschlechtskrankheiten der Universität Würzburg, Würzburg, Germany; and
Max-Planck-Institut für Immunbiologie, Freiburg, Germany
We have analyzed in vivo effects of the murine IL-4 mutant
Q116D/Y119D (QY), which forms unproductive complexes with IL-4R
and
is an antagonist for IL-4 and IL-13 in vitro. Treatment of BALB/c mice
with QY during immunization with OVA completely inhibited synthesis of
OVA-specific IgE and IgG1. BALB/c-derived knockout mice lacking either
IL-4 or IL-4R also did not develop specific IgE or IgG1, but mounted
a much stronger IgG2a and IgG2b response than wild-type mice. In
contrast, QY treatment of normal BALB/c mice suppressed specific IgG2a,
IgG2b, and IgG3 synthesis, which may indicate the development of
tolerance toward the allergen. Associated with the lack of IgE
synthesis in QY-treated wild-type mice and in
IL-4-/- mice used as a control was the failure to
develop immediate cutaneous hypersensitivity or anaphylactic shock upon
rechallenge. Interestingly, QY treatment also inhibited humoral immune
responses and allergic reactivity in SJL/J mice, a strain that did not
produce IgE, but displayed IgE-independent mast cell degranulation
mediated by specific IgG1. We conclude that QY inhibits Ag-specific
humoral immune responses and allergic symptoms mediated either by IgE
or IgG1. It needs to be clarified how QY abrogates synthesis of IgG2a,
IgG2b, and IgG3, but the induction of tolerance toward nonhazardous
protein Ags should be advantageous for therapy of atopic disorders and
other Th2-dominated diseases.
This article has been cited by other articles:
|
|
 |
|
  J. Xiang, J. Rir-Sim-Ah, and Y. Tesfaigzi IL-9 and IL-13 Induce Mucous Cell Metaplasia That Is Reduced by IFN-{gamma} in a Bax-Mediated Pathway Am. J. Respir. Cell Mol. Biol., March 1, 2008; 38(3): 310 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Karras, J. R. Crosby, M. Guha, D. Tung, D. A. Miller, W. A. Gaarde, R. S. Geary, B. P. Monia, and S. A. Gregory Anti-Inflammatory Activity of Inhaled IL-4 Receptor-{alpha} Antisense Oligonucleotide in Mice Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 276 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-L. Andrews, J. W. Holloway, S. T. Holgate, and D. E. Davies IL-4 Receptor {alpha} Is an Important Modulator of IL-4 and IL-13 Receptor Binding: Implications for the Development of Therapeutic Targets. J. Immunol., June 15, 2006; 176(12): 7456 - 7461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Yao, W. Chen, H. Luo, Q. Jiang, Z. Xia, L. Zang, J. Zuo, X. Wei, Z. Chen, X. Shen, et al. Identification of core functional region of murine IL-4 using peptide phage display and molecular modeling Int. Immunol., January 1, 2006; 18(1): 19 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Knoops, J. Louahed, J. Van Snick, and J.-C. Renauld IL-9 Promotes but Is Not Necessary for Systemic Anaphylaxis J. Immunol., July 1, 2005; 175(1): 335 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Matheson, V. J. Johnson, and M. I. Luster Immune Mediators in a Murine Model for Occupational Asthma: Studies with Toluene Diisocyanate Toxicol. Sci., March 1, 2005; 84(1): 99 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kulka and D. D. Metcalfe High-resolution tracking of cell division demonstrates differential effects of TH1 and TH2 cytokines on SCF-dependent human mast cell production in vitro:correlation with apoptosis and Kit expression Blood, January 15, 2005; 105(2): 592 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zamorano, M. D. Rivas, A. Garcia-Trinidad, C.-K. Qu, and A. D. Keegan Phosphatidylcholine-Specific Phospholipase C Activity Is Necessary for the Activation of STAT6 J. Immunol., October 15, 2003; 171(8): 4203 - 4209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N.J. McKenzie and P. G. Fallon Decoy Receptors in the Regulation of T Helper Cell Type 2 Responses J. Exp. Med., March 17, 2003; 197(6): 675 - 679. [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Bracken, K. Belanger, W. O. Cookson, E. Triche, D. C. Christiani, and B. P. Leaderer Genetic and Perinatal Risk Factors for Asthma Onset and Severity: A Review and Theoretical Analysis Epidemiol. Rev., December 1, 2002; 24(2): 176 - 189. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Matheson, R. Lemus, R. W. Lange, M. H. Karol, and M. I. Luster Role of Tumor Necrosis Factor in Toluene Diisocyanate Asthma Am. J. Respir. Cell Mol. Biol., October 1, 2002; 27(4): 396 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Litterst and E. Pfitzner An LXXLL Motif in the Transactivation Domain of STAT6 Mediates Recruitment of NCoA-1/SRC-1 J. Biol. Chem., September 20, 2002; 277(39): 36052 - 36060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Perez-G., M. Melo, A. D. Keegan, and J. Zamorano Aspirin and Salicylates Inhibit the IL-4- and IL-13-Induced Activation of STAT6 J. Immunol., February 1, 2002; 168(3): 1428 - 1434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J-C Renauld New insights into the role of cytokines in asthma J. Clin. Pathol., August 1, 2001; 54(8): 577 - 589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. G. Tournoy, J. C. Kips, and R. A. Pauwels The Allergen-Induced Airway Hyperresponsiveness in a Human-Mouse Chimera Model of Asthma Is T Cell and IL-4 and IL-5 Dependent J. Immunol., June 1, 2001; 166(11): 6982 - 6991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tomkinson, C. Duez, G. Cieslewicz, J. C. Pratt, A. Joetham, M.-C. Shanafelt, R. Gundel, and E. W. Gelfand A Murine IL-4 Receptor Antagonist That Inhibits IL-4- and IL-13-Induced Responses Prevents Antigen-Induced Airway Eosinophilia and Airway Hyperresponsiveness J. Immunol., May 1, 2001; 166(9): 5792 - 5800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. T Holgate Science, medicine, and the future: Allergic disorders BMJ, January 22, 2000; 320(7229): 231 - 234. [Full Text]
|
|
|
|
|
|
L. Cohn, R. J. Homer, H. MacLeod, M. Mohrs, F. Brombacher, and K. Bottomly Th2-Induced Airway Mucus Production Is Dependent on IL-4R{alpha}, But Not on Eosinophils J. Immunol., May 15, 1999; 162(10): 6178 - 6183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, F. E. R. Simons, and K. T. HayGlass Environmental Antigen-Induced IL-13 Responses Are Elevated Among Subjects with Allergic Rhinitis, Are Independent of IL-4, and Are Inhibited by Endogenous IFN-{gamma} Synthesis J. Immunol., December 15, 1998; 161(12): 7007 - 7014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Justice, J. Crosby, M. T. Borchers, A. Tomkinson, J. J. Lee, and N. A. Lee CD4+ T cell-dependent airway mucus production occurs in response to IL-5 expression in lung Am J Physiol Lung Cell Mol Physiol, May 1, 2002; 282(5): L1066 - L1074. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
