title: Microbial heat shock protein 65 attenuates airway hyperresponsiveness and inflammation by modulating the function of dendritic cells.
abstract: Heat shock proteins (HSPs), produced in response to stress, are suppressive in disease models. We previously showed that Mycobacterium leprae HSP65 prevented development of airway hyperresponsiveness and inflammation in mice. Our goal in this study was to define the mechanism responsible for the suppressive effects of HSP. In one in vivo approach, BALB/c mice were sensitized to OVA, followed by primary OVA challenges. Several weeks later, HSP65 was administered prior to a single, provocative secondary challenge. In a second in vivo approach, the secondary challenge was replaced by intratracheal instillation of allergen-pulsed bone marrow-derived dendritic cells (BMDCs). The in vitro effects of HSP65 on BMDCs were examined in coculture experiments with CD4(+) T cells. In vivo, HSP65 prevented the development of airway hyperresponsiveness and inflammation. Additionally, Th1 cytokine levels in bronchoalveolar lavage fluid were increased. In vitro, HSP65 induced Notch receptor ligand Delta1 expression on BMDCs, and HSP65-treated BMDCs skewed CD4(+) T cells to Th1 cytokine production. Thus, HSP65-induced effects on allergen-induced airway hyperresponsiveness and inflammation were associated with increased Delta1 expression on dendritic cells, modulation of dendritic cell function, and CD4(+) Th1 cytokine production.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: Yi Yeong
authors.initials: YY
authors.lastname: Jeong
authors.forename: Joanne
authors.initials: J
authors.lastname: Domenico
authors.forename: Yi
authors.initials: Y
authors.lastname: Jia
authors.forename: Junyan
authors.initials: J
authors.lastname: Han
authors.forename: Ralf
authors.initials: R
authors.lastname: Spallek
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lucas
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000502:physiology*; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009166:Mycobacterium leprae / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; C074119:heat-shock protein 65, Mycobacterium; D010047:Ovalbumin