PMID- 30098789
OWN - NLM
STAT- MEDLINE
DCOM- 20190513
LR  - 20190513
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 503
IP  - 3
DP  - 2018 Sep 10
TI  - A novel MtHSP70-FPR1 fusion protein enhances cytotoxic T lymphocyte responses to 
      cervical cancer cells by activating human monocyte-derived dendritic cells via 
      the p38 MAPK signaling pathway.
PG  - 2108-2116
LID - S0006-291X(18)31671-1 [pii]
LID - 10.1016/j.bbrc.2018.07.167 [doi]
AB  - OBJECTIVE: To evaluate the potential effects of recombinant mycobacterium 
      tuberculosis heat shock protein 70-formyl peptide receptor 1 (MtHSP70-FPR1) 
      fusion protein on human monocyte-derived dendritic cell (moDC) maturation; 
      cytotoxic T lymphocyte (CTL) responses to cervical cancer (CC) cells; and the 
      roles of the p38 MAPK, ERK, and JNK pathways in its transition. METHODS: 
      Monocytes were positively selected with a MACS column with antiCD14 
      antibody-conjugated microbeads from umbilical cord blood. MoDCs were stimulated 
      with MtHSP70-FPR1, MtHSP70, a mix of MtHSP70 and FPR1, FPR1, or phosphate buffer 
      solution (PBS) as control. Flow cytometry was used to analyze the surface 
      molecule expression of moDCs and IFN-gamma-producing CD8(+) T cells. T cell 
      proliferation was assessed using [3][H]-thymidine assays. The cytotoxicity of 
      moDC-activated T cells against CC cells was evaluated by MTT assays. Cytokine 
      production was determined by enzyme-linked immunosorbent assay. Western blotting 
      was used to investigate protein expression. RESULTS: Compared with MtHSP70, 
      MtHSP70 + FPR1, FPR1, or PBS-mediated moDCs, MtHSP70-FPR1-pulsed moDCs expressed 
      higher levels of CD80, CD86, CD83, HLA-DR, and CCR7; secreted more IL-12p70, 
      TNF-a and IL-1beta; and elicited stronger CTL priming and proliferation, resulting 
      in an effective, HLA-I-dependent killing effect on CC cells. The p38 MAPK, ERK, 
      and JNK pathways were all activated in MtHSP70-FPR1-mediated moDC maturation, but 
      the p38 MAPK pathway played a vital role. CONCLUSIONS: The excellent capability 
      of MtHSP70-FPR1 fusion protein to induce phenotypical and functional maturation 
      of moDCs and CC-specific CTL responses partly illustrates the potential clinical 
      benefits of DC-based immunotherapy for CC.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Xiao, Meizhu
AU  - Xiao M
AD  - Department of Obstetrics and Gynecology, Beijing Chaoyang Hospital, Capital 
      Medical University, China.
FAU - Feng, Ying
AU  - Feng Y
AD  - Department of Obstetrics and Gynecology, Beijing Chaoyang Hospital, Capital 
      Medical University, China.
FAU - Cao, Guangming
AU  - Cao G
AD  - Department of Obstetrics and Gynecology, Beijing Chaoyang Hospital, Capital 
      Medical University, China.
FAU - Liu, Chongdong
AU  - Liu C
AD  - Department of Obstetrics and Gynecology, Beijing Chaoyang Hospital, Capital 
      Medical University, China.
FAU - Zhang, Zhenyu
AU  - Zhang Z
AD  - Department of Obstetrics and Gynecology, Beijing Chaoyang Hospital, Capital 
      Medical University, China. Electronic address: zhenyuzhang2000@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180808
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Receptors, Formyl Peptide)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Dendritic Cells/metabolism
MH  - Female
MH  - HSP70 Heat-Shock Proteins/chemistry/*metabolism
MH  - Humans
MH  - Lipopolysaccharide Receptors
MH  - Monocytes/metabolism
MH  - Mycobacterium tuberculosis/*chemistry/metabolism
MH  - Receptors, Formyl Peptide/chemistry/*metabolism
MH  - *Signal Transduction
MH  - T-Lymphocytes, Cytotoxic/*metabolism
MH  - Uterine Cervical Neoplasms/*metabolism/pathology
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
OTO - NOTNLM
OT  - Cervical cancer
OT  - Cytotoxic T lymphocyte
OT  - MAPKs pathway
OT  - Maturation
OT  - Monocyte-derived dentritic cells
OT  - MtHSP70-FPR1
EDAT- 2018/08/14 06:00
MHDA- 2019/05/14 06:00
CRDT- 2018/08/13 06:00
PHST- 2018/07/22 00:00 [received]
PHST- 2018/07/31 00:00 [accepted]
PHST- 2018/08/14 06:00 [pubmed]
PHST- 2019/05/14 06:00 [medline]
PHST- 2018/08/13 06:00 [entrez]
AID - S0006-291X(18)31671-1 [pii]
AID - 10.1016/j.bbrc.2018.07.167 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Sep 10;503(3):2108-2116. doi: 
      10.1016/j.bbrc.2018.07.167. Epub 2018 Aug 8.