Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.

Victor Matheu; Alexandra Treschow; Ingrid Teige; Vaidrius Navikas; Shohreh Issazadeh-Navikas

doi:10.1186/1465-9921-6-25

Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.

Victor Matheu, Alexandra Treschow, Ingrid Teige, Vaidrius Navikas, Shohreh Issazadeh-Navikas

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

8 Citationer (Scopus)

Abstract

Udgivelsesdato: 2005-null

Originalsprog	Engelsk
Tidsskrift	Respiratory research
Vol/bind	6
Sider (fra-til)	25
DOI	https://doi.org/10.1186/1465-9921-6-25
Status	Udgivet - 2005

Bibliografisk note

Keywords: Adjuvants, Immunologic; Animals; CpG Islands; Cytokines; Disease Models, Animal; Female; Interferon-beta; Mice; Mice, Knockout; Oligodeoxyribonucleotides; Ovalbumin; Respiratory Hypersensitivity; Treatment Outcome

Adgang til dokumentet

10.1186/1465-9921-6-25

Citationsformater

@article{c356036057c911dd8d9f000ea68e967b,

title = "Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.",

abstract = "BACKGROUND: CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects of CpG-ODN is not known. OBJECTIVE: Here, we aimed to elucidate the role of IFN-beta in the anti-allergic effect of CpG motifs. METHODS: We assessed the immune response in OVA-primed/OVA-challenged IFN-beta knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment with synthetic CpG motifs. RESULTS: Vaccination with CpG-ODN reduced the number of cells in airways of OVA-sensitized WT but not IFN-beta-/- mice. Although airway eosinophilia was reduced in both treated groups, they were significantly higher in IFN-beta-/- mice. Other inflammatory cells, such as lymphocytes and macrophages were enhanced in airways by CpG treatment in IFN-beta-/- mice. The ratio of IFN-gamma/IL-4 cytokines in airways was significantly skewed to a Th1 response in WT compared to IFN-beta-/- group. In contrast, IL-4 and IgE were reduced with no differences between groups. Ag-specific T-cell proliferation, Th1-cytokines such as IFN-gamma, IL-2 and also IL-12 were significantly lower in IFN-beta-/- mice. Surprisingly, we discovered that intranasal treatment of mice with CpG-ODN results in mild synovitis particularly in IFN-beta-/- mice. CONCLUSION: Our results indicate that induction of Th1 response by therapy with CpG-ODN is only slightly and partially dependent on IFN-beta, while IFN-beta is not an absolute requirement for suppression of airway eosinophilia and IgE. Furthermore, our finding of mild synovitis is a warning for possible negative effects of CpG-ODN vaccination.",

author = "Victor Matheu and Alexandra Treschow and Ingrid Teige and Vaidrius Navikas and Shohreh Issazadeh-Navikas",

note = "Keywords: Adjuvants, Immunologic; Animals; CpG Islands; Cytokines; Disease Models, Animal; Female; Interferon-beta; Mice; Mice, Knockout; Oligodeoxyribonucleotides; Ovalbumin; Respiratory Hypersensitivity; Treatment Outcome",

year = "2005",

doi = "10.1186/1465-9921-6-25",

language = "English",

volume = "6",

pages = "25",

journal = "Respiratory Research (Print)",

issn = "1465-9921",

publisher = "BioMed Central Ltd.",

}

TY - JOUR

T1 - Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.

AU - Matheu, Victor

AU - Treschow, Alexandra

AU - Teige, Ingrid

AU - Navikas, Vaidrius

AU - Issazadeh-Navikas, Shohreh

N1 - Keywords: Adjuvants, Immunologic; Animals; CpG Islands; Cytokines; Disease Models, Animal; Female; Interferon-beta; Mice; Mice, Knockout; Oligodeoxyribonucleotides; Ovalbumin; Respiratory Hypersensitivity; Treatment Outcome

PY - 2005

Y1 - 2005

N2 - BACKGROUND: CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects of CpG-ODN is not known. OBJECTIVE: Here, we aimed to elucidate the role of IFN-beta in the anti-allergic effect of CpG motifs. METHODS: We assessed the immune response in OVA-primed/OVA-challenged IFN-beta knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment with synthetic CpG motifs. RESULTS: Vaccination with CpG-ODN reduced the number of cells in airways of OVA-sensitized WT but not IFN-beta-/- mice. Although airway eosinophilia was reduced in both treated groups, they were significantly higher in IFN-beta-/- mice. Other inflammatory cells, such as lymphocytes and macrophages were enhanced in airways by CpG treatment in IFN-beta-/- mice. The ratio of IFN-gamma/IL-4 cytokines in airways was significantly skewed to a Th1 response in WT compared to IFN-beta-/- group. In contrast, IL-4 and IgE were reduced with no differences between groups. Ag-specific T-cell proliferation, Th1-cytokines such as IFN-gamma, IL-2 and also IL-12 were significantly lower in IFN-beta-/- mice. Surprisingly, we discovered that intranasal treatment of mice with CpG-ODN results in mild synovitis particularly in IFN-beta-/- mice. CONCLUSION: Our results indicate that induction of Th1 response by therapy with CpG-ODN is only slightly and partially dependent on IFN-beta, while IFN-beta is not an absolute requirement for suppression of airway eosinophilia and IgE. Furthermore, our finding of mild synovitis is a warning for possible negative effects of CpG-ODN vaccination.

AB - BACKGROUND: CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects of CpG-ODN is not known. OBJECTIVE: Here, we aimed to elucidate the role of IFN-beta in the anti-allergic effect of CpG motifs. METHODS: We assessed the immune response in OVA-primed/OVA-challenged IFN-beta knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment with synthetic CpG motifs. RESULTS: Vaccination with CpG-ODN reduced the number of cells in airways of OVA-sensitized WT but not IFN-beta-/- mice. Although airway eosinophilia was reduced in both treated groups, they were significantly higher in IFN-beta-/- mice. Other inflammatory cells, such as lymphocytes and macrophages were enhanced in airways by CpG treatment in IFN-beta-/- mice. The ratio of IFN-gamma/IL-4 cytokines in airways was significantly skewed to a Th1 response in WT compared to IFN-beta-/- group. In contrast, IL-4 and IgE were reduced with no differences between groups. Ag-specific T-cell proliferation, Th1-cytokines such as IFN-gamma, IL-2 and also IL-12 were significantly lower in IFN-beta-/- mice. Surprisingly, we discovered that intranasal treatment of mice with CpG-ODN results in mild synovitis particularly in IFN-beta-/- mice. CONCLUSION: Our results indicate that induction of Th1 response by therapy with CpG-ODN is only slightly and partially dependent on IFN-beta, while IFN-beta is not an absolute requirement for suppression of airway eosinophilia and IgE. Furthermore, our finding of mild synovitis is a warning for possible negative effects of CpG-ODN vaccination.

U2 - 10.1186/1465-9921-6-25

DO - 10.1186/1465-9921-6-25

M3 - Journal article

C2 - 15748290

VL - 6

SP - 25

JO - Respiratory Research (Print)

JF - Respiratory Research (Print)

SN - 1465-9921

ER -