Upregulation of p55 and p75 Receptors Mediating TNF-α Transport Across the Injured Blood-Spinal Cord Barrier
| Autor: | Abba J. Kastin, Weihong Pan, Balazs Csernus |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Receptor expression Down-Regulation Inflammation Biology Blood–brain barrier Receptors Tumor Necrosis Factor Iodine Radioisotopes Mice Cellular and Molecular Neuroscience Downregulation and upregulation Antigens CD Internal medicine Genes Regulator Animals Outbred Strains medicine Animals Receptors Tumor Necrosis Factor Type II RNA Messenger Receptor Spinal Cord Injuries Mice Knockout Tumor Necrosis Factor-alpha General Medicine Myelitis Neuroregeneration Up-Regulation Mice Inbred C57BL Protein Transport medicine.anatomical_structure Endocrinology Transcytosis Blood-Brain Barrier Receptors Tumor Necrosis Factor Type I Knockout mouse Immunology medicine.symptom |
| Zdroj: | Journal of Molecular Neuroscience. 21:173-184 |
| ISSN: | 0895-8696 |
| DOI: | 10.1385/jmn:21:2:173 |
| Popis: | Tumor necrosis factor (TNF-alpha) is involved in the inflammation and tissue regeneration occurring after spinal cord injury (SCI). This study tests the specific role of p55 and p75 receptors in mediating the transport of TNF-alpha across the blood-spinal cord barrier (BSCB) after SCI by compression. Transcytosis of 125I-TNF-alpha across a monolayer of the cerebral endothelial cells that compose the blood-brain barrier was significantly reduced in the absence of functional p55 and p75 receptors. At 3 d after SCI, double receptor knockout mice had a significantly reduced increase in TNF-alpha uptake from blood to injured lumbar spinal cord as compared with their inbred controls, despite the similar extent of BSCB disruption (measured by 99mTc-albumin). The p75 single receptor knockout mice had a reduced increase in 125I-TNF-alpha uptake, whereas the p55 receptor knockout mice had no significant increase of 125I-TNF-alpha uptake after SCI, suggesting that the p55 receptor plays a major role. Hence, the increased uptake of TNF-alpha 3 d after SCI is not explained by nonspecific barrier disruption but by receptor-mediated upregulation of transport. Quantitative RT-PCR analysis further showed that upregulation of TNF-alpha transport was related to increased expression of mRNA for p55 and p75 receptors. The increase of p55 receptor expression was more robust and seen between 12 h and 1 wk after SCI, whereas the increase of p75 receptor expression occurred later and involved fewer regions. Thus, the differential upregulation of p55 and p75 receptors indicates that permeation of TNF-alpha across the injured BSCB remains a regulated process. Knowledge of receptor-mediated regulation could facilitate effective therapeutic manipulation of BSCB permeation of vascular cytokines important to CNS regeneration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink