Cargando…
Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice
BACKGROUND: Microglia/macrophages are known to play important roles in initiating brain inflammation after spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) have been proven to play a critical part in several inflammatory diseases through regulation of both...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220802/ https://www.ncbi.nlm.nih.gov/pubmed/24289479 http://dx.doi.org/10.1186/1742-2094-10-141 |
_version_ | 1782342785339228160 |
---|---|
author | Xu, ChangJun Wang, Tao Cheng, Si Liu, YuGuang |
author_facet | Xu, ChangJun Wang, Tao Cheng, Si Liu, YuGuang |
author_sort | Xu, ChangJun |
collection | PubMed |
description | BACKGROUND: Microglia/macrophages are known to play important roles in initiating brain inflammation after spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) have been proven to play a critical part in several inflammatory diseases through regulation of both adaptive and innate immune responses. Tim-3 can be expressed by microglia/macrophages and regulates their function in the innate immune response. However, the effect of Tim-3 on inflammatory responses following ICH is unclear. METHODS: In this study, we investigated Tim-3 expression, the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and brain water content in peri-hematomal brain tissue at 12 hours and at 1, 3, 5, and 7 days post-ICH in wild type (WT) ICH and Tim-3(−/−) ICH mice. The numbers of Tim-3 positive cells,astrocytes, neutrophils and microglia/macrophages were detected using immunofluorescence staining. Cytokines were measured by ELISA. Double immunoflurorescence labeling was performed to identify the cellular source of Tim-3 expression. Mouse neurological deficit scores were assessed through animal behavior. RESULTS: Expression of Tim-3 increased early in mouse peri-hematomal brain tissue after autologous blood injection, peaked at day 1, and was positively correlated with the concentrations of TNF-α, IL-1β, and brain water content. Tim-3 was predominantly expressed in microglia/macrophages. Compared with WT mice, Tim-3(−/−) mice had reduced ICH-induced brain inflammation with decreased TNF-α and IL-1β, cerebral edema and neurological deficit scores. Moreover, Tim-/- inhibited activation of microglia/macrophages. The number of activated microglia/macrophages in Tim-3(−/−) ICH mice was much lower than that in WT ICH mice. CONCLUSIONS: Our findings demonstrate that Tim-3 plays an important role in brain inflammation after ICH, and may be a potential treatment target. |
format | Online Article Text |
id | pubmed-4220802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42208022014-11-06 Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice Xu, ChangJun Wang, Tao Cheng, Si Liu, YuGuang J Neuroinflammation Research BACKGROUND: Microglia/macrophages are known to play important roles in initiating brain inflammation after spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) have been proven to play a critical part in several inflammatory diseases through regulation of both adaptive and innate immune responses. Tim-3 can be expressed by microglia/macrophages and regulates their function in the innate immune response. However, the effect of Tim-3 on inflammatory responses following ICH is unclear. METHODS: In this study, we investigated Tim-3 expression, the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and brain water content in peri-hematomal brain tissue at 12 hours and at 1, 3, 5, and 7 days post-ICH in wild type (WT) ICH and Tim-3(−/−) ICH mice. The numbers of Tim-3 positive cells,astrocytes, neutrophils and microglia/macrophages were detected using immunofluorescence staining. Cytokines were measured by ELISA. Double immunoflurorescence labeling was performed to identify the cellular source of Tim-3 expression. Mouse neurological deficit scores were assessed through animal behavior. RESULTS: Expression of Tim-3 increased early in mouse peri-hematomal brain tissue after autologous blood injection, peaked at day 1, and was positively correlated with the concentrations of TNF-α, IL-1β, and brain water content. Tim-3 was predominantly expressed in microglia/macrophages. Compared with WT mice, Tim-3(−/−) mice had reduced ICH-induced brain inflammation with decreased TNF-α and IL-1β, cerebral edema and neurological deficit scores. Moreover, Tim-/- inhibited activation of microglia/macrophages. The number of activated microglia/macrophages in Tim-3(−/−) ICH mice was much lower than that in WT ICH mice. CONCLUSIONS: Our findings demonstrate that Tim-3 plays an important role in brain inflammation after ICH, and may be a potential treatment target. BioMed Central 2013-12-01 /pmc/articles/PMC4220802/ /pubmed/24289479 http://dx.doi.org/10.1186/1742-2094-10-141 Text en Copyright © 2013 Xu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Xu, ChangJun Wang, Tao Cheng, Si Liu, YuGuang Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice |
title | Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice |
title_full | Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice |
title_fullStr | Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice |
title_full_unstemmed | Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice |
title_short | Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice |
title_sort | increased expression of t cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220802/ https://www.ncbi.nlm.nih.gov/pubmed/24289479 http://dx.doi.org/10.1186/1742-2094-10-141 |
work_keys_str_mv | AT xuchangjun increasedexpressionoftcellimmunoglobulinandmucindomain3aggravatesbraininflammationviaregulationofthefunctionofmicrogliamacrophagesafterintracerebralhemorrhageinmice AT wangtao increasedexpressionoftcellimmunoglobulinandmucindomain3aggravatesbraininflammationviaregulationofthefunctionofmicrogliamacrophagesafterintracerebralhemorrhageinmice AT chengsi increasedexpressionoftcellimmunoglobulinandmucindomain3aggravatesbraininflammationviaregulationofthefunctionofmicrogliamacrophagesafterintracerebralhemorrhageinmice AT liuyuguang increasedexpressionoftcellimmunoglobulinandmucindomain3aggravatesbraininflammationviaregulationofthefunctionofmicrogliamacrophagesafterintracerebralhemorrhageinmice |