Stimulation of allergen-loaded macrophages by TLR9-ligand potentiates IL-10-mediated suppression of allergic airway inflammation in mice
<p>Abstract</p> <p>Background</p> <p>Previously, we demonstrated that OVA-loaded macrophages (OVA-Mφ) partially suppress OVA-induced airway manifestations of asthma in BALB/c mice. <it>In vitro </it>studies showed that OVA-Mφ start to produce IL-10 upon inte...
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| Format: | Article |
| Language: | English |
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BMC
2004-11-01
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| Series: | Respiratory Research |
| Online Access: | http://respiratory-research.com/content/5/1/21 |
| _version_ | 1818641544204255232 |
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| author | Hofman Gerard A Jeurink Prescilla V van Esch Betty CAM Vissers Joost LM van Oosterhout Antoon JM |
| author_facet | Hofman Gerard A Jeurink Prescilla V van Esch Betty CAM Vissers Joost LM van Oosterhout Antoon JM |
| author_sort | Hofman Gerard A |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Previously, we demonstrated that OVA-loaded macrophages (OVA-Mφ) partially suppress OVA-induced airway manifestations of asthma in BALB/c mice. <it>In vitro </it>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 <it>in vivo</it>, and whether <it>ex vivo </it>stimulation of the IL-10 production by OVA-Mφ could enhance these effects.</p> <p>Methods</p> <p>Peritoneal Mφ were loaded with OVA and stimulated with LPS or immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) <it>in vitro</it>. The increase of IL-10 production was examined and, subsequently, <it>ex vivo </it>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<sup>-/- </sup>mice were used for treatment.</p> <p>Results</p> <p>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<sup>-/-</sup>Mφ that were loaded with OVA and stimulated with ISS-ODN <it>ex vivo</it>, failed to suppress OVA-induced airway inflammation.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-16T23:28:51Z |
| format | Article |
| id | doaj.art-0bbea0779e89486eae375f7531d41494 |
| institution | Directory Open Access Journal |
| issn | 1465-9921 |
| language | English |
| last_indexed | 2024-12-16T23:28:51Z |
| publishDate | 2004-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-0bbea0779e89486eae375f7531d414942022-12-21T22:11:56ZengBMCRespiratory Research1465-99212004-11-01512110.1186/1465-9921-5-21Stimulation of allergen-loaded macrophages by TLR9-ligand potentiates IL-10-mediated suppression of allergic airway inflammation in miceHofman Gerard AJeurink Prescilla Vvan Esch Betty CAMVissers Joost LMvan Oosterhout Antoon JM<p>Abstract</p> <p>Background</p> <p>Previously, we demonstrated that OVA-loaded macrophages (OVA-Mφ) partially suppress OVA-induced airway manifestations of asthma in BALB/c mice. <it>In vitro </it>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 <it>in vivo</it>, and whether <it>ex vivo </it>stimulation of the IL-10 production by OVA-Mφ could enhance these effects.</p> <p>Methods</p> <p>Peritoneal Mφ were loaded with OVA and stimulated with LPS or immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) <it>in vitro</it>. The increase of IL-10 production was examined and, subsequently, <it>ex vivo </it>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<sup>-/- </sup>mice were used for treatment.</p> <p>Results</p> <p>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<sup>-/-</sup>Mφ that were loaded with OVA and stimulated with ISS-ODN <it>ex vivo</it>, failed to suppress OVA-induced airway inflammation.</p> <p>Conclusions</p> <p>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.</p>http://respiratory-research.com/content/5/1/21 |
| spellingShingle | Hofman Gerard A Jeurink Prescilla V van Esch Betty CAM Vissers Joost LM van Oosterhout Antoon JM Stimulation of allergen-loaded macrophages by TLR9-ligand potentiates IL-10-mediated suppression of allergic airway inflammation in mice Respiratory Research |
| title | Stimulation of allergen-loaded macrophages by TLR9-ligand potentiates IL-10-mediated suppression of allergic airway inflammation in mice |
| title_full | Stimulation of allergen-loaded macrophages by TLR9-ligand potentiates IL-10-mediated suppression of allergic airway inflammation in mice |
| title_fullStr | Stimulation of allergen-loaded macrophages by TLR9-ligand potentiates IL-10-mediated suppression of allergic airway inflammation in mice |
| title_full_unstemmed | Stimulation of allergen-loaded macrophages by TLR9-ligand potentiates IL-10-mediated suppression of allergic airway inflammation in mice |
| title_short | Stimulation of allergen-loaded macrophages by TLR9-ligand potentiates IL-10-mediated suppression of allergic airway inflammation in mice |
| title_sort | stimulation of allergen loaded macrophages by tlr9 ligand potentiates il 10 mediated suppression of allergic airway inflammation in mice |
| url | http://respiratory-research.com/content/5/1/21 |
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