PMID- 29974377
OWN - NLM
STAT- MEDLINE
DCOM- 20190411
LR  - 20190411
IS  - 1573-2568 (Electronic)
IS  - 0163-2116 (Linking)
VI  - 63
IP  - 12
DP  - 2018 Dec
TI  - Effect of Homocysteine on the Differentiation of CD4(+) T Cells into Th17 Cells.
PG  - 3339-3347
LID - 10.1007/s10620-018-5177-2 [doi]
AB  - BACKGROUND: The hyperhomocysteinaemia (Hhcy) is a common phenomenon observed in 
      patients with inflammatory bowel disease (IBD). Our previous study showed that 
      Hhcy aggravated intestinal inflammation in an animal model of colitis. Increased 
      levels of IL-17 and RORgammat were also observed in this animal model of colitis with 
      Hhcy. However, the direct effect of homocysteine on the differentiation of Th17 
      cells has never been studied. The aim of this study was to investigate the direct 
      effect of Hhcy on the differentiation of CD4(+) T cells into Th17 cells. METHOD: 
      Lamina propria lymphocytes (LPLs) in colonic mucosa of Wistar rats were isolated 
      and cultured under Th17-inducing (iTH17) environments. Different concentrations 
      of the Hcy (0-100 mumol/ml) were added alone or combined with IL-23 (100 ng/ml) or 
      folate (5 mumol/ml). The LPLs were divided into eight groups as follows: (1) 
      Control group; (2) 10 mumol/ml Hcy group; (3) 25 mumol/ml Hcy group; (4) 50 mumol/ml 
      Hcy group; (5) 100 mumol/ml Hcy group; (6) 100 ng/ml IL-23 group; (7) 50 mumol/ml 
      Hcy + 100 ng/ml IL-23 group and (8) 50 mumol/ml Hcy + 100 ng/ml IL-23 + 5 mumol/ml 
      folate group. The protein expression levels of IL-17, retinoid-related orphan 
      nuclear receptor-gammat (RORgammat), p38 MAPK, phosphorylated p38 MAPK, cytosolic 
      phospholipase A2 (cPLA2), phosphorylated-cPLA2 and cyclooxygenase 2 (COX2) were 
      detected by immunoblot analysis. The protein level of prostaglandin E2 (PGE2) and 
      IL-17 was detected by ELISA, and IL-17 and RORgammat-positive CD4(+) T cells were 
      stained and analyzed by flow cytometry. RESULTS: Hcy increased the protein levels 
      of IL-17, RORgammat, the ratio of phosphorylated p38 MAPK to p38 MAPK (p-p38/p38), 
      the ratio of phosphorylated cPLA2 to cPLA2 (p-cPLA2/cPLA2) and COX2. The effect 
      was concentration dependent to a certain degree; Hcy of 50 mumol/ml was the 
      optimal concentration to increase the protein levels of those molecules. The 
      level of IL-17 and PGE2 in the cell culture supernatants and the expression of 
      IL-17 and RORgammat in positive CD4(+) T cells were also increased in the group of 
      Hhcy. IL-23 showed a cooperative effect with Hcy on the differentiation of CD4(+) 
      Th cells into Th17 cells, whereas folate supplementation showed an inhibition 
      action. CONCLUSIONS: Homocysteine promoted the differentiation of CD4(+) T cells 
      into Th17 cells in a dose-dependant manner. This effect could be inhibited by 
      folate.
FAU - Gao, Xin
AU  - Gao X
AD  - Department of Gastroenterology, Zhongnan Hospital, Wuhan University School of 
      Medicine, Donghu Road 169, Wuhan, 430071, People's Republic of China.
AD  - The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, 
      Wuhan, 430071, People's Republic of China.
FAU - Li, Jin
AU  - Li J
AD  - Department of Gastroenterology, Zhongnan Hospital, Wuhan University School of 
      Medicine, Donghu Road 169, Wuhan, 430071, People's Republic of China.
AD  - The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, 
      Wuhan, 430071, People's Republic of China.
FAU - Chen, Min
AU  - Chen M
AUID- ORCID: 0000-0001-8248-5408
AD  - Department of Gastroenterology, Zhongnan Hospital, Wuhan University School of 
      Medicine, Donghu Road 169, Wuhan, 430071, People's Republic of China. 
      chenmin8106@whu.edu.cn.
AD  - The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, 
      Wuhan, 430071, People's Republic of China. chenmin8106@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180704
PL  - United States
TA  - Dig Dis Sci
JT  - Digestive diseases and sciences
JID - 7902782
RN  - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 12001-76-2 (Vitamin B Complex)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Ptgs2 protein, rat)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.1.4 (Group IV Phospholipases A2)
RN  - EC 3.1.1.4 (Pla2g4a protein, rat)
SB  - IM
CIN - Dig Dis Sci. 2018 Dec;63(12):3161-3163. PMID: 30191498
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*physiology
MH  - *Cell Differentiation/drug effects/physiology
MH  - Colon/metabolism/pathology
MH  - Cyclooxygenase 2/metabolism
MH  - Disease Models, Animal
MH  - Folic Acid/*pharmacology
MH  - Group IV Phospholipases A2/metabolism
MH  - Homocysteine/*metabolism
MH  - *Hyperhomocysteinemia/drug therapy/etiology/metabolism
MH  - *Inflammatory Bowel Diseases/complications/metabolism
MH  - Mucous Membrane/metabolism/pathology
MH  - Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Th17 Cells/*physiology
MH  - Treatment Outcome
MH  - Vitamin B Complex/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - Folate
OT  - Homocysteine
OT  - IL-23
OT  - Inflammatory bowel disease
OT  - Interleukin-17
EDAT- 2018/07/06 06:00
MHDA- 2019/04/12 06:00
CRDT- 2018/07/06 06:00
PHST- 2017/10/10 00:00 [received]
PHST- 2018/06/22 00:00 [accepted]
PHST- 2018/07/06 06:00 [pubmed]
PHST- 2019/04/12 06:00 [medline]
PHST- 2018/07/06 06:00 [entrez]
AID - 10.1007/s10620-018-5177-2 [pii]
AID - 10.1007/s10620-018-5177-2 [doi]
PST - ppublish
SO  - Dig Dis Sci. 2018 Dec;63(12):3339-3347. doi: 10.1007/s10620-018-5177-2. Epub 2018 
      Jul 4.