PMID- 26163174
OWN - NLM
STAT- MEDLINE
DCOM- 20160113
LR  - 20150928
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 288
IP  - 2
DP  - 2015 Oct 15
TI  - Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration 
      in experimental silicosis.
PG  - 152-60
LID - S0041-008X(15)30029-6 [pii]
LID - 10.1016/j.taap.2015.07.002 [doi]
AB  - BACKGROUND: Silicosis is a systemic disease caused by inhaling silicon dioxide 
      (SiO2). Phagocytosis of SiO2 in the lung initiates an inflammatory cascade that 
      results in fibroblast proliferation and migration and subsequent fibrosis. 
      Clinical evidence indicates that the activation of alveolar macrophages by SiO2 
      produces rapid and sustained inflammation that is characterized by the generation 
      of monocyte chemotactic protein 1 (MCP-1), which induces fibrosis. Pulmonary 
      fibroblast-derived MCP-1 may play a critical role in fibroblast proliferation and 
      migration. METHODS AND RESULTS: Experiments using primary cultured adult human 
      pulmonary fibroblasts (HPF-a) demonstrated the following results: 1) SiO2 
      treatment resulted in the rapid and sustained induction of MCP-1 as well as the 
      elevation of the CC chemokine receptor type 2 (CCR2) protein levels; 2) 
      pretreatment of HPF-a with RS-102895, a specific CCR2 inhibitor, abolished the 
      SiO2-induced increase in cell activation and migration in both 2D and 3D culture 
      systems; and 3) RNA interference targeting CCR2 prevented the SiO2-induced 
      increase in cell migration. CONCLUSION: These data demonstrated that the 
      up-regulation of pulmonary fibroblast-derived MCP-1 is involved in pulmonary 
      fibroblast migration induced by SiO2. CCR2 was also up-regulated in response to 
      SiO2, and this up-regulation facilitated the effect of MCP-1 on fibroblasts. Our 
      study deciphered the link between fibroblast-derived MCP-1 and SiO2-induced cell 
      migration. This finding provides novel insight into the potential of MCP-1 in the 
      development of novel therapeutic strategies for silicosis.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Liu, Xueting
AU  - Liu X
AD  - Department of Physiology, Medical School of Southeast University, Nanjing, 
      Jiangsu 210009, China.
FAU - Fang, Shencun
AU  - Fang S
AD  - Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 
      210029, China.
FAU - Liu, Haijun
AU  - Liu H
AD  - Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical 
      University, Nanjing, Jiangsu 210009, China.
FAU - Wang, Xingang
AU  - Wang X
AD  - Department of Physiology, Medical School of Southeast University, Nanjing, 
      Jiangsu 210009, China.
FAU - Dai, Xiaoniu
AU  - Dai X
AD  - Department of Physiology, Medical School of Southeast University, Nanjing, 
      Jiangsu 210009, China.
FAU - Yin, Qing
AU  - Yin Q
AD  - Department of Physiology, Medical School of Southeast University, Nanjing, 
      Jiangsu 210009, China.
FAU - Yun, Tianwei
AU  - Yun T
AD  - Department of Physiology, Medical School of Southeast University, Nanjing, 
      Jiangsu 210009, China.
FAU - Wang, Wei
AU  - Wang W
AD  - Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 
      210029, China.
FAU - Zhang, Yingming
AU  - Zhang Y
AD  - Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 
      210029, China.
FAU - Liao, Hong
AU  - Liao H
AD  - Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical 
      University, Nanjing, Jiangsu 210009, China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Physiology, Medical School of Southeast University, Nanjing, 
      Jiangsu 210009, China.
FAU - Yao, Honghong
AU  - Yao H
AD  - Department of Pharmacology, Medical School of Southeast University, Nanjing, 
      Jiangsu 210009, China.
FAU - Chao, Jie
AU  - Chao J
AD  - Department of Physiology, Medical School of Southeast University, Nanjing, 
      Jiangsu 210009, China. Electronic address: chaojie@seu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150708
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 7631-86-9 (Silicon Dioxide)
SB  - IM
MH  - *Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Fibroblasts/drug effects/*metabolism/pathology
MH  - Humans
MH  - Lung/drug effects/*metabolism/pathology
MH  - Pulmonary Fibrosis/chemically induced/genetics/*metabolism/pathology
MH  - RNA Interference
MH  - Receptors, CCR2/antagonists & inhibitors/genetics/metabolism
MH  - Signal Transduction
MH  - Silicon Dioxide/toxicity
MH  - Silicosis/genetics/*metabolism/pathology
MH  - Time Factors
MH  - Transfection
MH  - Up-Regulation
OTO - NOTNLM
OT  - CCR2
OT  - Fibroblast
OT  - MCP-1
OT  - MCPIP1
OT  - Migration
OT  - Silicosis
EDAT- 2015/07/15 06:00
MHDA- 2016/01/14 06:00
CRDT- 2015/07/12 06:00
PHST- 2015/02/25 00:00 [received]
PHST- 2015/06/28 00:00 [revised]
PHST- 2015/07/02 00:00 [accepted]
PHST- 2015/07/12 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/01/14 06:00 [medline]
AID - S0041-008X(15)30029-6 [pii]
AID - 10.1016/j.taap.2015.07.002 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2015 Oct 15;288(2):152-60. doi: 
      10.1016/j.taap.2015.07.002. Epub 2015 Jul 8.