PMID- 30681198
OWN - NLM
STAT- MEDLINE
DCOM- 20200717
LR  - 20200717
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 120
IP  - 6
DP  - 2019 Jun
TI  - The immunomodulatory mechanism of brain injury induced by hyperhomocysteinemia in 
      spontaneously hypertensive rats.
PG  - 9421-9429
LID - 10.1002/jcb.28217 [doi]
AB  - BACKGROUND: Elevated plasma homocysteine (Hcy) concentration is considered as the 
      diagnostic criteria of Hyperhomocysteinemia (HHcy), which is associated with the 
      inflammatory response and blood-brain barrier disruption. Previous studies have 
      proposed that HHcy with hypertension was associated with the brain injury by 
      enhancing the cerebrovascular permeability, however, the immune mechanism remains 
      obscure. The purpose of the study is to explore the immunomodulatory mechanism of 
      brain injury in spontaneously hypertensive rats (SHRs) induced by HHcy. MATERIALS 
      AND METHODS: Sixty SHRs were randomly assigned to three groups: SHR-C (control 
      group), SHR-M (methionine group) and SHR-T (treatment group). Physical 
      examination of body weight, systolic blood pressure (SBP) and plasma Hcy content 
      was measured every 4 weeks. Besides, T-helper cell 17 and regulatory T cells 
      (Treg)-related inflammatory cytokines (interleukin [IL]-6, IL-17, IL-10, and 
      transforming growth factor beta [TGF-beta]) and genes (RORgammat and FoxP3) were 
      detected by enzyme-linked immunosorbent assay, quantitative polymerase chain 
      reaction , Western blot, and immunohistochemistry. RESULTS: High methionine diet 
      could cause weight loss, SBP rising, and plasma Hcy content significantly 
      elevated. IL-16 and IL-17A levels in peripheral blood and in brain tissue both 
      lifted, while IL-10 and TGF-beta levels dropped; RORgammat expression raised in brain, 
      nevertheless, FoxP3 levels were the opposite. After the intervention with vitamin 
      B6, B12, and folic acid in SHR-T group, these trends would be eased or completely 
      changed. Furthermore, brain tissue slices showed that IL-17-positive cells tended 
      to decrease, and IL-10-positive cells increased in SHR-T group, which was 
      reversed in SHR-M group. CONCLUSIONS: HHcy may promote inflammation that can lead 
      to brain lesions and down-regulate immune response to protect the brain.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Department of Geriatric, the Second Hospital of Tianjin Medical University, 
      Tianjin, China.
FAU - Wang, Lin
AU  - Wang L
AD  - Department of Geriatric, the Second Hospital of Tianjin Medical University, 
      Tianjin, China.
FAU - Zhou, Xin
AU  - Zhou X
AD  - Department of Cardiovascular disease and heart center, Pingjin Hospital, 
      Logistics university of the Chinese people's armed police forces, Tianjin, China.
FAU - Geng, Jie
AU  - Geng J
AD  - Department of Cardiology, Tianjin Chest Hospital, Tianjin, China.
FAU - Li, Xin
AU  - Li X
AUID- ORCID: 0000-0001-6449-4044
AD  - Department of Geriatric, the Second Hospital of Tianjin Medical University, 
      Tianjin, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190125
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, rat)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-6)
RN  - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 130068-27-8 (Interleukin-10)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/drug effects/immunology
MH  - Brain Injuries/*diet therapy/etiology/immunology/pathology
MH  - Forkhead Transcription Factors/genetics
MH  - Homocysteine/blood
MH  - Humans
MH  - Hyperhomocysteinemia/blood/complications/*diet therapy/immunology
MH  - Immunomodulation/genetics/immunology
MH  - Inflammation/*diet therapy/etiology/genetics/immunology
MH  - Interleukin-10/genetics
MH  - Interleukin-17/genetics
MH  - Interleukin-6/genetics
MH  - Methionine/pharmacology
MH  - Nuclear Receptor Subfamily 1, Group F, Member 3/genetics
MH  - Rats
MH  - Rats, Inbred SHR/blood/*genetics/immunology
MH  - T-Lymphocytes, Helper-Inducer/drug effects/immunology
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Transforming Growth Factor beta/genetics
OTO - NOTNLM
OT  - brain injury
OT  - homocysteine
OT  - immune mechanism
OT  - spontaneously hypertensive rats
EDAT- 2019/01/27 06:00
MHDA- 2020/07/18 06:00
CRDT- 2019/01/26 06:00
PHST- 2018/10/08 00:00 [received]
PHST- 2018/11/15 00:00 [accepted]
PHST- 2019/01/27 06:00 [pubmed]
PHST- 2020/07/18 06:00 [medline]
PHST- 2019/01/26 06:00 [entrez]
AID - 10.1002/jcb.28217 [doi]
PST - ppublish
SO  - J Cell Biochem. 2019 Jun;120(6):9421-9429. doi: 10.1002/jcb.28217. Epub 2019 Jan 
      25.