HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xu, J. Articles by Corry, D. B. Search for Related Content PubMed PubMed Citation Articles by Xu, J. Articles by Corry, D. B.

Endogenous Attenuation of Allergic Lung Inflammation by Syndecan-1¹

Jie Xu^*, Pyong Woo Park^2,*,,,¶, Farrah Kheradmand^2,*,¶ and David B. Corry^2,*,,¶

Departments of ^* Medicine, Molecular and Cellular Biology, Molecular Virology and Microbiology, Immunology, and ^¶ Biology of Inflammation Center, Baylor College of Medicine, Houston, TX 77030

The airway plays a vital role in allergic lung diseases by responding to inhaled allergens and initiating allergic inflammation. Various proinflammatory functions of the airway epithelium have been identified, but, equally important, anti-inflammatory mechanisms must also exist. We show in this study that syndecan-1, the major heparan sulfate proteoglycan of epithelial cells, attenuates allergic lung inflammation. Our results show that syndecan-1-null mice instilled with allergens exhibit exaggerated airway hyperresponsiveness, glycoprotein hypersecretion, eosinophilia, and lung IL-4 responses. However, administration of purified syndecan-1 ectodomains, but not ectodomain core proteins devoid of heparan sulfate, significantly inhibits these inflammatory responses. Furthermore, syndecan-1 ectodomains are shed into the airway when wild-type mice are intranasally instilled with several biochemically distinct inducers of allergic lung inflammation. Our results also show that syndecan-1 ectodomains bind to the CC chemokines (CCL7, CCL11, and CCL17) implicated in allergic diseases, inhibit CC chemokine-mediated T cell migration, and suppress allergen-induced accumulation of Th2 cells in the lung through their heparan sulfate chains. Together, these findings uncover an endogenous anti-inflammatory mechanism of the airway epithelium where syndecan-1 ectodomains attenuate allergic lung inflammation via suppression of CC chemokine-mediated Th2 cell recruitment to the lung.

This article has been cited by other articles:

				S. C. H. Chan, V. O. Y. Leung, M. S. M. Ip, and D. K. Y. Shum Shed Syndecan-1 Restricts Neutrophil Elastase from {alpha}1-Antitrypsin in Neutrophilic Airway Inflammation Am. J. Respir. Cell Mol. Biol., November 1, 2009; 41(5): 620 - 628. [Abstract] [Full Text] [PDF]

				K. Hayashida, W. C. Parks, and P. W. Park Syndecan-1 shedding facilitates the resolution of neutrophilic inflammation by removing sequestered CXC chemokines Blood, October 1, 2009; 114(14): 3033 - 3043. [Abstract] [Full Text] [PDF]

				B. K. Masouleh, G. B. Ten Dam, M. K. Wild, R. Seelige, J. van der Vlag, A. L. Rops, F. G. Echtermeyer, D. Vestweber, T. H. van Kuppevelt, L. Kiesel, et al. Role of the Heparan Sulfate Proteoglycan Syndecan-1 (CD138) in Delayed-Type Hypersensitivity J. Immunol., April 15, 2009; 182(8): 4985 - 4993. [Abstract] [Full Text] [PDF]

				K. Hayashida, P. D. Stahl, and P. W. Park Syndecan-1 Ectodomain Shedding Is Regulated by the Small GTPase Rab5 J. Biol. Chem., December 19, 2008; 283(51): 35435 - 35444. [Abstract] [Full Text] [PDF]

				K. Hayashida, Y. Chen, A. H. Bartlett, and P. W. Park Syndecan-1 Is an in Vivo Suppressor of Gram-positive Toxic Shock J. Biol. Chem., July 18, 2008; 283(29): 19895 - 19903. [Abstract] [Full Text] [PDF]

				Y. Chen, A. Hayashida, A. E. Bennett, S. K. Hollingshead, and P. W. Park Streptococcus pneumoniae Sheds Syndecan-1 Ectodomains through ZmpC, a Metalloproteinase Virulence Factor J. Biol. Chem., January 5, 2007; 282(1): 159 - 167. [Abstract] [Full Text] [PDF]

				K. J. Greenlee, D. B. Corry, D. A. Engler, R. K. Matsunami, P. Tessier, R. G. Cook, Z. Werb, and F. Kheradmand Proteomic Identification of In Vivo Substrates for Matrix Metalloproteinases 2 and 9 Reveals a Mechanism for Resolution of Inflammation J. Immunol., November 15, 2006; 177(10): 7312 - 7321. [Abstract] [Full Text] [PDF]

				K. Hayashida, D. R. Johnston, O. Goldberger, and P. W. Park Syndecan-1 Expression in Epithelial Cells Is Induced by Transforming Growth Factor beta through a PKA-dependent Pathway J. Biol. Chem., August 25, 2006; 281(34): 24365 - 24374. [Abstract] [Full Text] [PDF]

				D. P. Beiting, P. W. Park, and J. A. Appleton Synthesis of Syndecan-1 by Skeletal Muscle Cells Is an Early Response to Infection with Trichinella spiralis but Is Not Essential for Nurse Cell Development Infect. Immun., March 1, 2006; 74(3): 1941 - 1943. [Abstract] [Full Text] [PDF]