Abstract
Background: Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-α, an important autocrine stimulator of dendritic cells and macrophages in the airways. Objective: We sought to study the mechanisms by which TNF-α and SP-D can affect cellular components of the pulmonary innate immune system. Methods: Cytokine and SP-D protein and mRNA expression was assessed by means of ELISA, Western blotting, and real-time PCR, respectively, by using in vivo models of allergic airway sensitization. Macrophage and dendritic cell phenotypes were analyzed by means of FACS analysis. Maturation of bone marrow-derived dendritic cells was investigated in vitro. Results: TNF-α, elicited either by allergen exposure or pulmonary overexpression, induced SP-D, IL-13, and mononuclear cell influx in the lung. Recombinant IL-13 by itself was also capable of enhancing SP-D in vivo and in vitro, and the SP-D response to allergen challenge was impaired in IL-13-deficient mice. Allergen-induced increase of SP-D in the airways coincided with resolution of TNF-α release and cell influx. SP-D-deficient mice had constitutively high numbers of alveolar mononuclear cells expressing TNF-α, MHC class II, CD86, and CD11b, characteristics of proinflammatory, myeloid dendritic cells. Recombinant SP-D significantly suppressed all of these molecules in bone marrow-derived dendritic cell cultures. Conclusions: TNF-α can contribute to enhanced SP-D production in the lung indirectly through inducing IL-13. SP-D, on the other hand, can antagonize the proinflammatory effects of TNF-α on macrophages and dendritic cells, at least partly, by inhibiting production of this cytokine.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 521-528 |
| Number of pages | 8 |
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 122 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2008 |
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Keywords
- airway inflammation
- dendritic cell
- mouse model
- SP-D
- TNF
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice. / Hortobágyi, László; Kierstein, Sonja; Krytska, Kateryna; Zhu, Xiaoping; Das, Anuk M.; Poulain, Francis R; Haczku, Angela Franciska.
In: Journal of Allergy and Clinical Immunology, Vol. 122, No. 3, 09.2008, p. 521-528.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice
AU - Hortobágyi, László
AU - Kierstein, Sonja
AU - Krytska, Kateryna
AU - Zhu, Xiaoping
AU - Das, Anuk M.
AU - Poulain, Francis R
AU - Haczku, Angela Franciska
PY - 2008/9
Y1 - 2008/9
N2 - Background: Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-α, an important autocrine stimulator of dendritic cells and macrophages in the airways. Objective: We sought to study the mechanisms by which TNF-α and SP-D can affect cellular components of the pulmonary innate immune system. Methods: Cytokine and SP-D protein and mRNA expression was assessed by means of ELISA, Western blotting, and real-time PCR, respectively, by using in vivo models of allergic airway sensitization. Macrophage and dendritic cell phenotypes were analyzed by means of FACS analysis. Maturation of bone marrow-derived dendritic cells was investigated in vitro. Results: TNF-α, elicited either by allergen exposure or pulmonary overexpression, induced SP-D, IL-13, and mononuclear cell influx in the lung. Recombinant IL-13 by itself was also capable of enhancing SP-D in vivo and in vitro, and the SP-D response to allergen challenge was impaired in IL-13-deficient mice. Allergen-induced increase of SP-D in the airways coincided with resolution of TNF-α release and cell influx. SP-D-deficient mice had constitutively high numbers of alveolar mononuclear cells expressing TNF-α, MHC class II, CD86, and CD11b, characteristics of proinflammatory, myeloid dendritic cells. Recombinant SP-D significantly suppressed all of these molecules in bone marrow-derived dendritic cell cultures. Conclusions: TNF-α can contribute to enhanced SP-D production in the lung indirectly through inducing IL-13. SP-D, on the other hand, can antagonize the proinflammatory effects of TNF-α on macrophages and dendritic cells, at least partly, by inhibiting production of this cytokine.
AB - Background: Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-α, an important autocrine stimulator of dendritic cells and macrophages in the airways. Objective: We sought to study the mechanisms by which TNF-α and SP-D can affect cellular components of the pulmonary innate immune system. Methods: Cytokine and SP-D protein and mRNA expression was assessed by means of ELISA, Western blotting, and real-time PCR, respectively, by using in vivo models of allergic airway sensitization. Macrophage and dendritic cell phenotypes were analyzed by means of FACS analysis. Maturation of bone marrow-derived dendritic cells was investigated in vitro. Results: TNF-α, elicited either by allergen exposure or pulmonary overexpression, induced SP-D, IL-13, and mononuclear cell influx in the lung. Recombinant IL-13 by itself was also capable of enhancing SP-D in vivo and in vitro, and the SP-D response to allergen challenge was impaired in IL-13-deficient mice. Allergen-induced increase of SP-D in the airways coincided with resolution of TNF-α release and cell influx. SP-D-deficient mice had constitutively high numbers of alveolar mononuclear cells expressing TNF-α, MHC class II, CD86, and CD11b, characteristics of proinflammatory, myeloid dendritic cells. Recombinant SP-D significantly suppressed all of these molecules in bone marrow-derived dendritic cell cultures. Conclusions: TNF-α can contribute to enhanced SP-D production in the lung indirectly through inducing IL-13. SP-D, on the other hand, can antagonize the proinflammatory effects of TNF-α on macrophages and dendritic cells, at least partly, by inhibiting production of this cytokine.
KW - airway inflammation
KW - dendritic cell
KW - mouse model
KW - SP-D
KW - TNF
UR - http://www.scopus.com/inward/record.url?scp=50649087257&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=50649087257&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2008.05.002
DO - 10.1016/j.jaci.2008.05.002
M3 - Article
C2 - 18554706
AN - SCOPUS:50649087257
VL - 122
SP - 521
EP - 528
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
ER -