title: Regulation of nasal airway homeostasis and inflammation in mice by SHP-1 and Th2/Th1 signaling pathways.
abstract: Allergic rhinitis is a chronic inflammatory disease orchestrated by Th2 lymphocytes. Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 is known to be a negative regulator in the IL-4α/STAT-6 signaling pathway of the lung. However, the role of SHP-1 enzyme and its functional relationship with Th2 and Th1 cytokines are not known in the nasal airway. In this study, we aimed to study the nasal inflammation as a result of SHP-1 deficiency in viable motheaten (mev) mice and to investigate the molecular mechanisms involved. Cytology, histology, and expression of cytokines and chemokines were analyzed to define the nature of the nasal inflammation. Targeted gene depletion of Th1 (IFN-γ) and Th2 (IL-4 and IL-13) cytokines was used to identify the critical pathways involved. Matrix metalloproteinases (MMPs) were studied to demonstrate the clearance mechanism of recruited inflammatory cells into the nasal airway. We showed here that mev mice had a spontaneous allergic rhinitis-like inflammation with eosinophilia, mucus metaplasia, up-regulation of Th2 cytokines (IL-4 and IL-13), chemokines (eotaxin), and MMPs. All of these inflammatory mediators were clearly counter-regulated by Th2 and Th1 cytokines. Deletion of IFN-γ gene induced a strong Th2-skewed inflammation with transepithelial migration of the inflammatory cells. These findings suggest that SHP-1 enzyme and Th2/Th1 paradigm may play a critical role in the maintenance of nasal immune homeostasis and in the regulation of allergic rhinitis.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Oh
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lane
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Joan
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Oh
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Seakwoo
authors.initials: S
authors.lastname: Lee
authors.affiliation: Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Tao
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D005780:Gelatin; D006706:Homeostasis / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D007371:Interferon-gamma / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008679:Metaplasia; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009093:Mucus / Q000378:metabolism; D017817:Nasal Lavage Fluid; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000172:deficiency / Q000378:metabolism*; D012220:Rhinitis / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D018925:Chemokines; D007371:Interferon-gamma; D005780:Gelatin; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
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