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- Title
Stimulation of allergen-loaded macrophages by TLR9-ligand potentiates IL-10-mediated suppression of allergic airway inflammation in mice.
- Authors
Vissers, Joost L. M.; Van Esch, Betty C. A. M.; Jeurink, Prescilla V.; Hofman, Gerard A.; Van Oosterhout, Antoon J. M.
- Abstract
Background: Previously, we demonstrated that OVA-loaded macrophages (OVA-Mϕ) partially suppress OVA-induced airway manifestations of asthma in BALB/c mice. In vitro studies showed that OVA-Mϕ start to produce IL-10 upon interaction with allergen-specific T cells, which might mediate their immunosuppressive effects. Herein, we examined whether IL-10 is essential for the immunosuppressive effects of OVA-Mϕ in vivo, and whether ex vivo stimulation of the IL-10 production by OVA-Mϕ could enhance these effects. Methods: Peritoneal Mϕ were loaded with OVA and stimulated with LPS or immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) in vitro. The increase of IL-10 production was examined and, subsequently, ex vivo stimulated OVA-Mϕ were used to treat (i.v.) OVA-sensitized mice. To further explore whether Mϕ-derived IL-10 mediates the immunosuppressive effects, Mϕ isolated from IL-10-/- mice were used for treatment. Results: We found that stimulation with LPS or ISS-ODN highly increased the IL-10 production by OVA-Mϕ (2.5-fold and 4.5-fold increase, respectively). ISS-ODN stimulation of OVA-Mϕ significantly potentiated the suppressive effects on allergic airway inflammation. Compared to sham-treatment, ISS-ODN-stimulated OVA-Mϕ suppressed the airway eosinophilia by 85% (vs. 30% by unstimulated OVA-Mϕ), IL-5 levels in bronchoalveolar lavage fluid by 80% (vs. 50%) and serum OVA-specific IgE levels by 60% (vs. 30%). Importantly, IL-10-/-Mϕ that were loaded with OVA and stimulated with ISS-ODN ex vivo, failed to suppress OVA-induced airway inflammation. Conclusions: These results demonstrate that Mϕ-derived IL-10 mediates anti-inflammatory responses in a mouse model of allergic asthma, which both can be potentiated by stimulation with ISS-ODN.
- Subjects
MACROPHAGES; ALLERGENS; LIGANDS (Biochemistry); INTERLEUKIN-10; AIRWAY (Anatomy); ALLERGIES; ASTHMA; LABORATORY mice; DISEASES
- Publication
Respiratory Research, 2004, Vol 5, p21
- ISSN
1465-9921
- Publication type
Article
- DOI
10.1186/1465-9921-5-21