Downstream Toll-like receptor signaling mediates adaptor-specific cytokine expression following focal cerebral ischemia
| Autor: | Maria Spatz, Modinat Lawal, Yongshan Mou, Bolanle M Famakin, John M. Hallenbeck |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Chemokine Toll-like Neutrophils medicine.medical_treatment Immunology Ischemia Granulocyte lcsh:RC346-429 Brain Ischemia Brain ischemia Mice Random Allocation Cellular and Molecular Neuroscience Internal medicine medicine Leukocytes Animals TRIF lcsh:Neurology. Diseases of the nervous system Focal ischemia Toll-like receptor biology General Neuroscience Research Toll-Like Receptors TLR signaling medicine.disease MyD88 medicine.anatomical_structure Endocrinology Cytokine Gene Expression Regulation Neurology Myeloid Differentiation Factor 88 biology.protein Cytokines Signal transduction MCAO Signal Transduction Receptor |
| Zdroj: | Journal of Neuroinflammation, Vol 9, Iss 1, p 174 (2012) Journal of Neuroinflammation |
| ISSN: | 1742-2094 |
| Popis: | Background Deletion of some Toll-like receptors (TLRs) affords protection against cerebral ischemia, but disruption of their known major downstream adaptors does not. To determine whether compensation in the production of downstream effectors by one pathway when the other is disrupted can explain these findings, we examined cytokine/chemokine expression and inflammatory infiltrates in wild-type (WT), MyD88−/− and TRIF-mutant mice following permanent middle cerebral artery occlusion (pMCAO). Methods Cytokine/chemokine expression was measured with a 25-plex bead array in the serum and brains of all three groups of mice at baseline (no surgery/naïve) and at 3 hours and 24 hours following pMCAO. Brain inflammatory and neutrophil infiltrates were examined 24 hours following pMCAO. Results IL-6, keratinocyte chemoattractant (KC), granulocyte colony-stimulating factor (G-CSF) and IL-10 were significantly decreased in MyD88−/− mice compared to WT mice following pMCAO. Significantly, decreased levels of the neutrophil chemoattractants KC and G-CSF corresponded with a trend toward fewer neutrophils in the brains of MyD88−/− mice. IP-10 was significantly decreased when either pathway was disrupted. MIP-1α was significantly decreased in TRIF-mutant mice, consistent with TRIF-dependent production. MyD88−/− mice showed elevations of a number of Th2 cytokines, such as IL-13, at baseline, which became significantly decreased following pMCAO. Conclusions Both MyD88 and TRIF mediate pathway-specific cytokine production following focal cerebral ischemia. Our results also suggest a compensatory Th2-type skew at baseline in MyD88−/− mice and a paradoxical switch to a Th1 phenotype following focal cerebral ischemia. The MyD88 pathway directs the expression of neutrophil chemoattractants following cerebral ischemia. |
| Databáze: | OpenAIRE |
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