title: Albumin induces neuroprotection against ischemic stroke by altering Toll-like receptor 4 and regulatory T cells in mice.
abstract: The objective of this study was to characterize the effect of albumin therapy on the expression of Toll-like receptor 4 (TLR 4), anti-inflammation cytokines and CD4(+)CD25(+)forkhead box P3 (Foxp3)(+) regulatory T lymphocytes (Treg cells) in the ischemic brain and peripheral immune system after Middle Cerebral Artery Occlusion (MCAO). Adult male Kunming mice were subjected to MCAO, the suture was withdrawn 2 h later followed by an intravenous administration of 25% albumin (1.25 g/kg) or saline (5 ml/kg) through caudal vein. We demonstrated that albumin administration elevated the serum albumin level supranormally at 6 h and 24 h after MCAO in mice. In addition, we showed that both in the ischemic brain and in the spleen, albumin administration significantly depressed the increase of TLR 4 mRNA expression by quantitative real-time polymerase chain reaction (QRT-PCR), and significantly increase the anti-inflammatory related interleukin-10 (IL-10) and transforming growth factor beta1 (TGF-β1) mRNA expression by transcription-polymerase chain reaction (RT-PCR) after MCAO. In the spleen, compared to sham group, strong TLR 4 immunoreactivity was noted in the saline group; while compared to saline group, albumin administration markedly reduced the immunoreactivity of TLR 4 after MCAO by immunohistochemistry. Moreover, albumin administration significantly increased the percentage of Treg in spleen CD4(+) cells by flow cytometry. In conclusion, the decrease of TLR 4 expression and the increase of Treg cell, IL-10, and TGF-β1 expression may partly contribute to the neuroprotective effect of albumin therapy on MCAO induced immune inflammatory responses.
authors: Department of Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors: Min
authors: M
authors: Wang
authors: Yongming
authors: Y
authors: Wang
authors: Jing
authors: J
authors: He
authors: Siyu
authors: S
authors: Wei
authors: Na
authors: N
authors: Zhang
authors: Fengyong
authors: F
authors: Liu
authors: Xin
authors: X
authors: Liu
authors: Yi
authors: Y
authors: Kang
authors: Xiaomei
authors: X
authors: Yao
mesh_terms: D000418:Albumins / Q000627:therapeutic use*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000418:Albumins; D015703:Antigens, CD; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D012709:Serum Albumin; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10