PMID- 31048100
OWN - NLM
STAT- MEDLINE
DCOM- 20191029
LR  - 20191029
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 111
DP  - 2019 Jul
TI  - Involvement of multiple transcription factors in regulation of IL-beta-induced MCP-1 
      expression in alveolar type II epithelial cells.
PG  - 95-105
LID - S0161-5890(19)30079-3 [pii]
LID - 10.1016/j.molimm.2019.04.013 [doi]
AB  - During acute lung injury, a large number of monocytes are recruited into the 
      pulmonary tissue, which is mainly mediated by local production of monocyte 
      chemotactic protein 1 (MCP-1). As an essential component of the lung tissues, 
      alveolar type II epithelial cells are one of the major sources of MCP-1. 
      Therefore, uncovering the mechanism whereby MCP-1 production is regulated in the 
      alveolar type II cells will provide a pivotal theoretical basis for clinical 
      intervention in acute lung injury. In the current study, we find that there is a 
      kappaB binding site in the MCP-1 promoter region, and mutation of the site leads to 
      reduced production of MCP-1 in alveolar type II epithelial cells. In contrast, 
      overexpression of NF-kappaB p65 significantly increases MCP-1 expression. 
      Furthermore, we elucidate that IKKalpha/beta-NF-kappaB p65 signaling pathway and 
      phosphorylation of serine 534 in NF-kappaB p65 are required for the maximal 
      expression of MCP-1. Also, Activator protein 1 (AP-1) site in the promoter region 
      and JNK1/2-c-Jun signaling are required for MCP-1 generation in alveolar type II 
      epithelial cells. Moreover, a CCAAT/enhancer-binding protein (C/EBP) element is 
      identified in the MCP-1 promoter region through the point mutation technique, and 
      further experiments demonstrate that both C/EBPbeta and C/EBPdelta are involved in basic 
      and IL-1beta-mediated MCP-1 expression. Of note, specificity protein 1-Sp1 
      expression is not changed in alveolar type II epithelial cells incubated with 
      IL-1beta, but it still control MCP-1 production by binding to the consensus sequence 
      in the promoter region. More importantly, we find that the results derived from 
      the cell line-MLE-12 cells and primary cells are consistent. Taken together, our 
      data provide insights into the molecular mechanism how MCP-1 expression in 
      inflammatory alveolar type II epithelial cells is regulated at transcription 
      level.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Yan, Chunguang
AU  - Yan C
AD  - Department of Pathogenic Biology and Immunology, Medical School of Southeast 
      University, Nanjing, 210009, China. Electronic address: ycgagcy@163.com.
FAU - Li, Bingyu
AU  - Li B
AD  - Department of Pathogenic Biology and Immunology, Medical School of Southeast 
      University, Nanjing, 210009, China. Electronic address: 1051678133@qq.com.
FAU - Liu, Xiufang
AU  - Liu X
AD  - Department of Pathogenic Biology and Immunology, Medical School of Southeast 
      University, Nanjing, 210009, China.
FAU - Deng, Chunming
AU  - Deng C
AD  - Department of Pathogenic Biology and Immunology, Medical School of Southeast 
      University, Nanjing, 210009, China.
FAU - Cai, Rentian
AU  - Cai R
AD  - Department of Infectious Diseases, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, 210006, China.
FAU - Shen, Yanfei
AU  - Shen Y
AD  - Department of Bioengineering, Medical School of Southeast University, Nanjing, 
      210009, China.
FAU - Tang, Huifang
AU  - Tang H
AD  - Zhejiang Respiratory Drugs Research Laboratory of the State Food and Drug 
      Administration of China, School of Medicine, Zhejiang University, Hangzhou, 
      Zhejiang 310058, China. Electronic address: tanghuifang@zju.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190429
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chemokine CCL2/*genetics
MH  - Epithelial Cells/*metabolism
MH  - I-kappa B Kinase/genetics
MH  - Inflammation/genetics
MH  - Interleukin-1beta/*genetics
MH  - Mice
MH  - NF-kappa B/genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Signal Transduction/genetics
MH  - Transcription Factor RelA/genetics
MH  - Transcription Factors/*genetics
MH  - Transcription, Genetic/genetics
OTO - NOTNLM
OT  - Acute lung inflammation
OT  - Alveolar type II epithelial cell
OT  - MCP-1
OT  - Transcription factors
EDAT- 2019/05/03 06:00
MHDA- 2019/10/30 06:00
CRDT- 2019/05/04 06:00
PHST- 2019/01/30 00:00 [received]
PHST- 2019/03/22 00:00 [revised]
PHST- 2019/04/23 00:00 [accepted]
PHST- 2019/05/03 06:00 [pubmed]
PHST- 2019/10/30 06:00 [medline]
PHST- 2019/05/04 06:00 [entrez]
AID - S0161-5890(19)30079-3 [pii]
AID - 10.1016/j.molimm.2019.04.013 [doi]
PST - ppublish
SO  - Mol Immunol. 2019 Jul;111:95-105. doi: 10.1016/j.molimm.2019.04.013. Epub 2019 
      Apr 29.