PMID- 27909722
OWN - NLM
STAT- MEDLINE
DCOM- 20170330
LR  - 20171116
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 15
IP  - 1
DP  - 2017 Jan
TI  - Expression of soluble programmed death-1 protein in peripheral blood regulatory T 
      cells and its effects on rheumatoid arthritis progression.
PG  - 460-466
LID - 10.3892/mmr.2016.5968 [doi]
AB  - The present study aimed to investigate the role of the soluble programmed death‑1 
      (sPD-1) protein, which is released by peripheral blood regulatory T cells (Treg) 
      during the progression of rheumatoid arthritis (RA). From October 2012 to May 
      2014, 82 RA patients (RA group) and 90 healthy volunteers (healthy controls; HC) 
      were recruited. Cluster of differentiation (CD)4, CD25 and forkhead/winged helix 
      transcription factor p3 (Foxp3) and expression of cytotoxic T lymphocyte 
      associated antigen 4 (CTLA-4) and Foxp3 were detected by flow cytometry. 
      Expression of sPD‑1 in Treg was detected by western blot analysis. 
      Immunosuppressive activity of CD4+CD25‑ Treg was measured via thiazolyl blue in 
      an MTT assay. ELISA was used to detect interleukin‑10 (IL‑10), transforming 
      growth factor beta (TGF-beta), interleukin-4 (IL-4), interferon‑gamma (IFN-gamma) and 
      nuclear factor of activated T cells (NF‑AT). It was observed that in peripheral 
      blood, CD4+CD25-FOXP3+/CD4+ levels were reduced in the RA group (P<0.001), and 
      sPD‑1 levels were markedly higher (P<0.001), compared with the HC group. 
      Additionally, it was observed that relative sPD‑1 protein expression in the small 
      interfering RNA (siRNA)-sPD-1 treated group was reduced compared with the 
      untreated and scrambled siRNA groups (all P<0.0001). The mean fluorescence 
      intensity of CTLA-4 and Foxp3 decreased markedly upon transfection with 
      siRNA-sPD-1 (P<0.001). Compared with the normal CD4+CD25‑ T group, optical 
      density (OD)540 values, IFN-gamma/IL-4 concentration ratio and NF‑AT activity in 
      siRNA untreated and scramble groups reduced significantly (all P<0.001). OD540 
      value, IFN-gamma/IL-4 concentration ratio and NF‑AT activity in the siRNA‑sPD‑1 group 
      were significantly upregulated (all P<0.001). Therefore, sPD-1 may suppress the 
      level of CD4+CD25‑ Tregs in the peripheral blood of RA patients, and may be 
      involved in a variety of immune processes mediated by CD4+CD25‑ Tregs.
FAU - Ren, Chun-Feng
AU  - Ren CF
AD  - Department of Rheumatism, The First People's Hospital of Jining, Jining, 
      Shangdong 272000, P.R. China.
FAU - Zhao, Ya-Xin
AU  - Zhao YX
AD  - Department of Pharmaceutical, The First People's Hospital of Jining, Jining, 
      Shangdong 272000, P.R. China.
FAU - Hou, Chun-Feng
AU  - Hou CF
AD  - Department of Rheumatism, The First People's Hospital of Jining, Jining, 
      Shangdong 272000, P.R. China.
FAU - Luan, Luan
AU  - Luan L
AD  - Department of Joint Surgery, The Affiliated Hospital of Jining Medical College, 
      Jining, Shangdong 272000, P.R. China.
FAU - Duan, Guo-Qing
AU  - Duan GQ
AD  - Department of Joint Surgery, The Affiliated Hospital of Jining Medical College, 
      Jining, Shangdong 272000, P.R. China.
FAU - Li, Shu-Jie
AU  - Li SJ
AD  - Department of Rheumatism, The First People's Hospital of Jining, Jining, 
      Shangdong 272000, P.R. China.
FAU - Zhao, Jian-Hong
AU  - Zhao JH
AD  - Department of Rheumatism, The First People's Hospital of Jining, Jining, 
      Shangdong 272000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20161128
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (CD4 Antigens)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (IL10 protein, human)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (Transforming Growth Factor beta)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Arthritis, Rheumatoid/immunology/*pathology
MH  - CD4 Antigens/immunology
MH  - CTLA-4 Antigen/immunology
MH  - Disease Progression
MH  - Female
MH  - Forkhead Transcription Factors/immunology
MH  - Humans
MH  - Immune Tolerance
MH  - Interferon-gamma/immunology
MH  - Interleukin-10/immunology
MH  - Interleukin-2 Receptor alpha Subunit/immunology
MH  - Male
MH  - Middle Aged
MH  - Programmed Cell Death 1 Receptor/*analysis/*immunology
MH  - T-Lymphocytes, Regulatory/immunology/*pathology
MH  - Transforming Growth Factor beta/immunology
EDAT- 2016/12/03 06:00
MHDA- 2017/03/31 06:00
CRDT- 2016/12/03 06:00
PHST- 2015/10/19 00:00 [received]
PHST- 2016/09/21 00:00 [accepted]
PHST- 2016/12/03 06:00 [pubmed]
PHST- 2017/03/31 06:00 [medline]
PHST- 2016/12/03 06:00 [entrez]
AID - 10.3892/mmr.2016.5968 [doi]
PST - ppublish
SO  - Mol Med Rep. 2017 Jan;15(1):460-466. doi: 10.3892/mmr.2016.5968. Epub 2016 Nov 
      28.