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*
Department of Dermatology and Allergy, University of Kiel, Kiel, Germany, and
St. John’s Institute of Dermatology, University of London, London, United Kingdom
A common feature of some parasitic infections and allergic and
atopic skin diseases is the involvement of Th2 lymphocytes and the
dermal appearance of eosinophils (Eos). Because Th2 lymphocytes
apparently do not release Eo attractants, we addressed the question of
whether the Th2 cytokine IL-4 induces its production in dermal
fibroblasts. We therefore stimulated fibroblasts with IL-4. HPLC
investigation of supernatants revealed a single Eo chemotactic protein,
which was purified to homogeneity giving a single 13-kDa band upon
SDS-PAGE analyses. Peptide mapping with subsequent amino acid
sequencing revealed an Eo-selective chemotaxin, which consists of a
mixture of N-terminally truncated and O-glycosylated forms
of the chemokine eotaxin. Other chemokines such as RANTES, MCP-3,
MCP-4, or MIP-1
were not detected as Eo chemotaxins under these
conditions. Using reverse transcriptase-PCR techniques, we found that
IL-4 dose and time dependently induces eotaxin mRNA in dermal
fibroblasts. Stimulation with IL-4 and TNF- caused a 10- to 20-fold
increase of the release of three biochemically different eotaxin forms,
each consisting of a mixture of N-terminally truncated and
O-glycosylated variants having the same backbone amino acid
sequence but different specific activities. Our findings support the
hypothesis that eosinophil recruitment seen in IL-4-mediated skin
reactions, at least in part, may be due to Th2 cytokine-mediated
induction of eotaxin in dermal fibroblasts.
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H. Nagase, M. Miyamasu, M. Yamaguchi, T. Fujisawa, K. Ohta, K. Yamamoto, Y. Morita, and K. Hirai Expression of CXCR4 in Eosinophils: Functional Analyses and Cytokine-Mediated Regulation J. Immunol., June 1, 2000; 164(11): 5935 - 5943. [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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A. Shinkai, H. Yoshisue, M. Koike, E. Shoji, S. Nakagawa, A. Saito, T. Takeda, S. Imabeppu, Y. Kato, N. Hanai, et al. A Novel Human CC Chemokine, Eotaxin-3, Which Is Expressed in IL-4-Stimulated Vascular Endothelial Cells, Exhibits Potent Activity Toward Eosinophils J. Immunol., August 1, 1999; 163(3): 1602 - 1610. [Abstract] [Full Text] [PDF]
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M. Miyamasu, M. Yamaguchi, T. Nakajima, Y. Misaki, Y. Morita, K. Matsushima, K. Yamamoto, and K. Hirai Th1-derived cytokine IFN-{gamma} is a potent inhibitor of eotaxin synthesis in vitro Int. Immunol., June 1, 1999; 11(6): 1001 - 1004. [Abstract] [Full Text]
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J. T. Wise, T. J. Baginski, and J. L. Mobley An Adoptive Transfer Model of Allergic Lung Inflammation in Mice Is Mediated by CD4+CD62LlowCD25+ T Cells J. Immunol., May 1, 1999; 162(9): 5592 - 5600. [Abstract] [Full Text] [PDF]
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S. Struyf, P. Proost, D. Schols, E. De Clercq, G. Opdenakker, J.-P. Lenaerts, M. Detheux, M. Parmentier, I. De Meester, S. Scharpe, et al. CD26/Dipeptidyl-Peptidase IV Down-Regulates the Eosinophil Chemotactic Potency, But Not the Anti-HIV Activity of Human Eotaxin by Affecting Its Interaction with CC Chemokine Receptor 3 J. Immunol., April 15, 1999; 162(8): 4903 - 4909. [Abstract] [Full Text] [PDF]
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J. Teruya-Feldstein, E. S. Jaffe, P. R. Burd, D. W. Kingma, J. E. Setsuda, and G. Tosato Differential Chemokine Expression in Tissues Involved by Hodgkin's Disease: Direct Correlation of Eotaxin Expression and Tissue Eosinophilia Blood, April 15, 1999; 93(8): 2463 - 2470. [Abstract] [Full Text] [PDF]
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L. M. Teran, M. Mochizuki, J. Bartels, E. L. Valencia, T. Nakajima, K. Hirai, and J.-M. Schröder Th1- and Th2-Type Cytokines Regulate the Expression and Production of Eotaxin and RANTES by Human Lung Fibroblasts Am. J. Respir. Cell Mol. Biol., April 1, 1999; 20(4): 777 - 786. [Abstract] [Full Text]
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L. Li, Y. Xia, A. Nguyen, Y. H. Lai, L. Feng, T. R. Mosmann, and D. Lo Effects of Th2 Cytokines on Chemokine Expression in the Lung: IL-13 Potently Induces Eotaxin Expression by Airway Epithelial Cells J. Immunol., March 1, 1999; 162(5): 2477 - 2487. [Abstract] [Full Text] [PDF]
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P. Loetscher, A. Pellegrino, J.-H. Gong, I. Mattioli, M. Loetscher, G. Bardi, M. Baggiolini, and I. Clark-Lewis The Ligands of CXC Chemokine Receptor 3, I-TAC, Mig, and IP10, Are Natural Antagonists for CCR3 J. Biol. Chem., January 26, 2001; 276(5): 2986 - 2991. [Abstract] [Full Text] [PDF]
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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]
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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]
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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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