title: Effect of microbial heat shock proteins on airway inflammation and hyperresponsiveness.
abstract: Microbial heat shock proteins (hsp) have been associated with the generation and induction of Th1-type immune responses. We tested the effects of treatment with five different microbial hsp (Mycobacterium leprae, Streptococcus pneumoniae, Helicobacter pylori, bacillus Calmette-Guérin, and Mycobacterium tuberculosis) in a murine model of allergic airway inflammation and airway hyperresponsiveness (AHR). Mice were sensitized to OVA by i.p. injection and then challenged by OVA inhalation. Hsp were administered to each group by i.p. injection before sensitization and challenge. Sensitized and challenged mice developed increased serum levels of OVA-specific IgE with significant airway eosinophilia and heightened responsiveness to methacholine when compared with nonsensitized animals. Administration of M. leprae hsp prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia in a dose-dependent manner. Treatment with M. leprae hsp also resulted in suppression of IL-4 and IL-5 production in bronchoalveolar lavage fluid, while IL-10 and IFN-gamma production were increased. Furthermore, M. leprae hsp treatment significantly suppressed OVA-specific IgE production and goblet cell hyperplasia/mucin hyperproduction. In contrast, treatment with the other hsp failed to prevent changes in airway responsiveness, lung eosinophilia, or cytokine production. Depletion of gamma/delta T lymphocytes before sensitization and challenge abolished the effect of M. leprae hsp treatment on AHR. These results indicate selective and distinctive properties among the hsp, and that M. leprae hsp may have a potential therapeutic role in the treatment of allergic airway inflammation and altered airway function.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: Yeong-Ho
authors.initials: YH
authors.lastname: Rha
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.forename: Angela
authors.initials: A
authors.lastname: Haczku
authors.forename: Anthony
authors.initials: A
authors.lastname: Joetham
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Catherine
authors.initials: C
authors.lastname: Duez
authors.forename: Marvin
authors.initials: M
authors.lastname: Siegel
authors.forename: M Kemal
authors.initials: MK
authors.lastname: Aydintug
authors.forename: Willi K
authors.initials: WK
authors.lastname: Born
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D001980:Bronchi / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology; D000939:Epitopes / Q000096:biosynthesis; D005260:Female; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006965:Hyperplasia; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D009077:Mucins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009166:Mycobacterium leprae / Q000502:physiology; D010047:Ovalbumin / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000382:microbiology / Q000517:prevention & control; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D000939:Epitopes; D006360:Heat-Shock Proteins; D015848:Interleukin-5; D009077:Mucins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin