دورية أكاديمية
Galectin-3 Modulates Microglia Inflammation in vitro but Not Neonatal Brain Injury in vivo under Inflammatory Conditions.
| العنوان: | Galectin-3 Modulates Microglia Inflammation in vitro but Not Neonatal Brain Injury in vivo under Inflammatory Conditions. |
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| المؤلفون: | Sävman K; Department of Pediatrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Department of Neonatology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden., Wang W; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Rafati AH; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Svedin P; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Nair S; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Golubinskaya V; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Ardalan M; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Brown KL; Department of Pediatrics, University of British Columbia and the British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada., Karlsson-Bengtsson A; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Mallard C; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. |
| المصدر: | Developmental neuroscience [Dev Neurosci] 2021; Vol. 43 (5), pp. 296-311. Date of Electronic Publication: 2021 Jun 15. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Karger Country of Publication: Switzerland NLM ID: 7809375 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1421-9859 (Electronic) Linking ISSN: 03785866 NLM ISO Abbreviation: Dev Neurosci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Basel, New York, Karger. |
| مواضيع طبية MeSH: | Brain Injuries* , Hypoxia-Ischemia, Brain*, Animals ; Animals, Newborn ; Galectin 3 ; Inflammation ; Lipopolysaccharides/toxicity ; Mice ; Microglia |
| مستخلص: | Microglia may contribute to injury but may also have neuroprotective properties. Galectin-3 has immunomodulatory properties that may affect the microglia phenotype and subsequent development of injury. Galectin-3 contributes to experimental hypoxic-ischemic (HI) injury in the neonatal brain, but it is unclear if galectin-3 has similar effects on infectious and sterile inflammation. Thus, we investigated the effect of galectin-3 on microglia in vitro under normal as well as infectious and sterile inflammatory conditions, and the effect of galectin-3 on neonatal brain injury following an infectious challenge in vivo. Conditions mimicking infectious or sterile inflammation were evaluated in primary microglia cell cultures from newborn mice, using LPS (10 ng/mL) and TNF-α (100 ng/mL). The response to galectin-3 was tested alone or together with LPS or TNF-α. Supernatants were collected 24 h after treatment and analyzed for 23 inflammatory mediators including pro- and anti-inflammatory cytokines and chemokines using multiplex protein analysis, as well as ELISA for MCP-1 and insulin-like growth factor (IGF)-1. Phosphorylation of proteins (AKT, ERK1/2, IκB-α, JNK, and p38) was determined in microglia cells. Neonatal brain injury was induced by a combination of LPS and HI (LPS + HI) in postnatal day 9 transgenic mice lacking functional galectin-3 and wild-type controls. LPS and TNF-α induced pro-inflammatory (9/11 vs. 9/10) and anti-inflammatory (6/6 vs. 2/6) cytokines, as well as chemokines (6/6 vs. 4/6) in a similar manner, except generally lower amplitude of the TNF-α-induced response. Galectin-3 alone had no effect on any of the proteins analyzed. Galectin-3 reduced the LPS- and TNF-α-induced microglia response for cytokines, chemokines, and phosphorylation of IκB-α. LPS decreased baseline IGF-1 levels, and the levels were restored by galectin-3. Brain injury or microglia response after LPS + HI was not affected by galectin-3 deficiency. Galectin-3 has no independent effect on microglia but modulates inflammatory activation in vitro. The effect was similar under infectious and sterile inflammatory conditions, suggesting that galectin-3 regulates inflammation not just by binding to LPS or toll-like receptor-4. Galectin-3 restores IGF-1 levels reduced by LPS-induced inflammation, suggesting a potential protective effect on infectious injury. However, galectin-3 deficiency did not affect microglia activation and was not beneficial in an injury model encompassing an infectious challenge. (© 2021 The Author(s). Published by S. Karger AG, Basel.) |
| فهرسة مساهمة: | Keywords: Brain injury; Cytokine; Hypoxia-ischemia; Inflammation; Insulin-like growth factor; Microglia |
| المشرفين على المادة: | 0 (Galectin 3) 0 (Lipopolysaccharides) |
| تواريخ الأحداث: | Date Created: 20210615 Date Completed: 20220127 Latest Revision: 20220127 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1159/000517687 |
| PMID: | 34130282 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1421-9859 |
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| DOI: | 10.1159/000517687 |