title: Endogenous attenuation of allergic lung inflammation by syndecan-1.
abstract: 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.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Pyong Woo
authors.initials: PW
authors.lastname: Park
authors.forename: Farrah
authors.initials: F
authors.lastname: Kheradmand
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
mesh_terms: D000276:Adjuvants, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000946:Antigens, Fungal / Q000008:administration & dosage; D001232:Aspergillus fumigatus / Q000276:immunology; D002464:Cell Migration Inhibition; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000378:metabolism; D017353:Gene Deletion; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D053668:Syndecan-1; D053667:Syndecans; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D000946:Antigens, Fungal; D019742:Chemokines, CC; D019812:Heparan Sulfate Proteoglycans; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011509:Proteoglycans; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D015847:Interleukin-4; D010047:Ovalbumin