Pivotal role of IL-6 in the hyperinflammatory responses to subacute ozone in adiponectin-deficient mice
| Autor: | Felippe Lazar Neto, Fernanda M. C. Ninin, Alison S. Williams, Joel A. Mathews, Norah G. Verbout, Allison P. Wurmbrand, David I. Kasahara, Stephanie A. Shore, Leandro A.P. Benedito, Hye Young Kim, Dale T. Umetsu, Christopher Hug |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Physiology Neutrophils T-Lymphocytes Inflammation Biology Mice Oxidants Photochemical Ozone Physiology (medical) Internal medicine Granulocyte Colony-Stimulating Factor Macrophages Alveolar medicine Animals Lymphocyte Count RNA Messenger Interleukin 6 Lung Mice Knockout Serum Amyloid A Protein Adiponectin Interleukin-6 Interleukin-17 Receptors Antigen T-Cell gamma-delta Cell Biology Articles Granulocyte colony-stimulating factor CCL20 Mice Inbred C57BL Endocrinology medicine.anatomical_structure Immunology biology.protein Interleukin 17 medicine.symptom Bronchoalveolar Lavage Fluid Hormone |
| Popis: | Adiponectin is an adipose-derived hormone with anti-inflammatory activity. Following subacute ozone exposure (0.3 ppm for 24–72 h), neutrophilic inflammation and IL-6 are augmented in adiponectin-deficient ( Adipo−/−) mice. The IL-17/granulocyte colony-stimulating factor (G-CSF) axis is required for this increased neutrophilia. We hypothesized that elevated IL-6 in Adipo−/−mice contributes to their augmented responses to ozone via effects on IL-17A expression. Therefore, we generated mice deficient in both adiponectin and IL-6 ( Adipo−/−/IL-6−/−) and exposed them to ozone or air. In ozone-exposed mice, bronchoalveolar lavage (BAL) neutrophils, IL-6, and G-CSF, and pulmonary Il17a mRNA expression were greater in Adipo−/−vs. wild-type mice, but reduced in Adipo−/−/IL-6−/−vs. Adipo−/−mice. IL-17A+F4/80+cells and IL-17A+γδ T cells were also reduced in Adipo−/−/IL-6−/−vs. Adipo−/−mice exposed to ozone. Only BAL neutrophils were reduced in IL-6−/−vs. wild-type mice. In wild-type mice, IL-6 was expressed in Gr-1+F4/80−CD11c−cells, whereas in Adipo−/−mice F4/80+CD11c+cells also expressed IL-6, suggesting that IL-6 is regulated by adiponectin in these alveolar macrophages. Transcriptomic analysis identified serum amyloid A3 ( Saa3), which promotes IL-17A expression, as the gene most differentially augmented by ozone in Adipo−/−vs. wild-type mice. After ozone, Saa3 mRNA expression was markedly greater in Adipo−/−vs. wild-type mice but reduced in Adipo−/−/IL-6−/−vs. Adipo−/−mice. In conclusion, our data support a pivotal role of IL-6 in the hyperinflammatory condition observed in Adipo−/−mice after ozone exposure and suggest that this role of IL-6 involves its ability to induce Saa3, IL-17A, and G-CSF. |
| Databáze: | OpenAIRE |
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