Eotaxin-2 induces monocytic apoptosis in patients who have undergone coronary artery bypass surgery and in THP-1 cells in vitro regulated by thrombomodulin

Yi Wen Lin, Chun Yao Huang, Chun Min Shih, Yi Ting Tsai, Chin Sheng Lin, Chih Yuan Lin, Chi Yuan Li, Shih Hurng Loh, Cheng Yen Lin, Feng Yen Lin, Chien Sung Tsai

研究成果: 雜誌貢獻文章

摘要

Cardiopulmonary bypass (CPB) induces cytokine production and causes postoperative monocytic inflammatory responses, which are associated with patient outcomes. In fact, monocytes regulate immunity through dynamic networks of survival and cellular apoptosis as well as thrombomodulin (TM)-associated differenciiation. Whether CPB affects the plasma level of eotaxin-2, a potent chemoattractant, or stimulates monocyte apoptosis among patients undergoing elective coronary artery bypass graft (CABG) surgery is also unknown. Thus, we aimed to investigate this subject and explored the feasible roles of TM in the phenomena. Firstly, clinical data showed that after CABG surgery, patients with lower plasma eotaxin-2 levels and higher TM expression levels exhibited reduced monocytic apoptosis, compared with that in patients with lower TM expression levels. Subsequently, to explore the hypothesis that eotaxin-2 induces monocytic apoptosis mediation by TM expression, we used in vitro monocytic THP1 cells. The results indicated that treatment of THP-1 cells with eotaxin-2 markedly increased apoptosis. Knockdown of TM significantly increased, and overexpression of TM significantly reversed eotaxin-2-induced monocyte apoptosis, which was compared with that of only eotaxin-2-treated THP-1 cells. TM may regulate mitochondria-mediated apoptosis by its PI3K/Akt axis signaling pathway, which acts as an extinguisher for p53 and BAX activation, as well as limit further downstream release of cytochrome c and cleavage of caspases 8 and 3; we suggest that TM interacts with the cofilin cytoskeleton, which further supports a role for TM in eotaxin-induced THP-1 cell apoptosis. Based on clinical observation and in vitro study, we conclude that TM expression on monocytes is associated with their apoptosis. The above mechanisms may be relevant to clinical phenomena in which patients exhibiting more monocytic apoptosis are complicated by higher plasma levels of eotaxin-2 and lower TM expression on monocytes after CABG surgery.
原文英語
文章編號AJTR0081221
頁(從 - 到)3133-3149
頁數17
期刊American Journal of Translational Research
10
發行號10
出版狀態已發佈 - 一月 1 2018

指紋

Chemokine CCL24
Thrombomodulin
Coronary Artery Bypass
Surgery
Apoptosis
Monocytes
Grafts
Cardiopulmonary Bypass
Transplants
Plasmas
In Vitro Techniques
Actin Depolymerizing Factors
Mitochondria
Caspase 8
Chemotactic Factors
Cytochromes c
Cytoskeleton

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

引用此文

Eotaxin-2 induces monocytic apoptosis in patients who have undergone coronary artery bypass surgery and in THP-1 cells in vitro regulated by thrombomodulin. / Lin, Yi Wen; Huang, Chun Yao; Shih, Chun Min; Tsai, Yi Ting; Lin, Chin Sheng; Lin, Chih Yuan; Li, Chi Yuan; Loh, Shih Hurng; Lin, Cheng Yen; Lin, Feng Yen; Tsai, Chien Sung.

於: American Journal of Translational Research, 卷 10, 編號 10, AJTR0081221, 01.01.2018, p. 3133-3149.

研究成果: 雜誌貢獻文章

Lin, Yi Wen ; Huang, Chun Yao ; Shih, Chun Min ; Tsai, Yi Ting ; Lin, Chin Sheng ; Lin, Chih Yuan ; Li, Chi Yuan ; Loh, Shih Hurng ; Lin, Cheng Yen ; Lin, Feng Yen ; Tsai, Chien Sung. / Eotaxin-2 induces monocytic apoptosis in patients who have undergone coronary artery bypass surgery and in THP-1 cells in vitro regulated by thrombomodulin. 於: American Journal of Translational Research. 2018 ; 卷 10, 編號 10. 頁 3133-3149.
@article{43431de4838b4557933f595c161822bf,
title = "Eotaxin-2 induces monocytic apoptosis in patients who have undergone coronary artery bypass surgery and in THP-1 cells in vitro regulated by thrombomodulin",
abstract = "Cardiopulmonary bypass (CPB) induces cytokine production and causes postoperative monocytic inflammatory responses, which are associated with patient outcomes. In fact, monocytes regulate immunity through dynamic networks of survival and cellular apoptosis as well as thrombomodulin (TM)-associated differenciiation. Whether CPB affects the plasma level of eotaxin-2, a potent chemoattractant, or stimulates monocyte apoptosis among patients undergoing elective coronary artery bypass graft (CABG) surgery is also unknown. Thus, we aimed to investigate this subject and explored the feasible roles of TM in the phenomena. Firstly, clinical data showed that after CABG surgery, patients with lower plasma eotaxin-2 levels and higher TM expression levels exhibited reduced monocytic apoptosis, compared with that in patients with lower TM expression levels. Subsequently, to explore the hypothesis that eotaxin-2 induces monocytic apoptosis mediation by TM expression, we used in vitro monocytic THP1 cells. The results indicated that treatment of THP-1 cells with eotaxin-2 markedly increased apoptosis. Knockdown of TM significantly increased, and overexpression of TM significantly reversed eotaxin-2-induced monocyte apoptosis, which was compared with that of only eotaxin-2-treated THP-1 cells. TM may regulate mitochondria-mediated apoptosis by its PI3K/Akt axis signaling pathway, which acts as an extinguisher for p53 and BAX activation, as well as limit further downstream release of cytochrome c and cleavage of caspases 8 and 3; we suggest that TM interacts with the cofilin cytoskeleton, which further supports a role for TM in eotaxin-induced THP-1 cell apoptosis. Based on clinical observation and in vitro study, we conclude that TM expression on monocytes is associated with their apoptosis. The above mechanisms may be relevant to clinical phenomena in which patients exhibiting more monocytic apoptosis are complicated by higher plasma levels of eotaxin-2 and lower TM expression on monocytes after CABG surgery.",
keywords = "Apoptosis, Eotaxin-2, Thrombomodulin",
author = "Lin, {Yi Wen} and Huang, {Chun Yao} and Shih, {Chun Min} and Tsai, {Yi Ting} and Lin, {Chin Sheng} and Lin, {Chih Yuan} and Li, {Chi Yuan} and Loh, {Shih Hurng} and Lin, {Cheng Yen} and Lin, {Feng Yen} and Tsai, {Chien Sung}",
year = "2018",
month = "1",
day = "1",
language = "English",
volume = "10",
pages = "3133--3149",
journal = "American Journal of Translational Research",
issn = "1943-8141",
publisher = "e-Century Publishing Corporation",
number = "10",

}

TY - JOUR

T1 - Eotaxin-2 induces monocytic apoptosis in patients who have undergone coronary artery bypass surgery and in THP-1 cells in vitro regulated by thrombomodulin

AU - Lin, Yi Wen

AU - Huang, Chun Yao

AU - Shih, Chun Min

AU - Tsai, Yi Ting

AU - Lin, Chin Sheng

AU - Lin, Chih Yuan

AU - Li, Chi Yuan

AU - Loh, Shih Hurng

AU - Lin, Cheng Yen

AU - Lin, Feng Yen

AU - Tsai, Chien Sung

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Cardiopulmonary bypass (CPB) induces cytokine production and causes postoperative monocytic inflammatory responses, which are associated with patient outcomes. In fact, monocytes regulate immunity through dynamic networks of survival and cellular apoptosis as well as thrombomodulin (TM)-associated differenciiation. Whether CPB affects the plasma level of eotaxin-2, a potent chemoattractant, or stimulates monocyte apoptosis among patients undergoing elective coronary artery bypass graft (CABG) surgery is also unknown. Thus, we aimed to investigate this subject and explored the feasible roles of TM in the phenomena. Firstly, clinical data showed that after CABG surgery, patients with lower plasma eotaxin-2 levels and higher TM expression levels exhibited reduced monocytic apoptosis, compared with that in patients with lower TM expression levels. Subsequently, to explore the hypothesis that eotaxin-2 induces monocytic apoptosis mediation by TM expression, we used in vitro monocytic THP1 cells. The results indicated that treatment of THP-1 cells with eotaxin-2 markedly increased apoptosis. Knockdown of TM significantly increased, and overexpression of TM significantly reversed eotaxin-2-induced monocyte apoptosis, which was compared with that of only eotaxin-2-treated THP-1 cells. TM may regulate mitochondria-mediated apoptosis by its PI3K/Akt axis signaling pathway, which acts as an extinguisher for p53 and BAX activation, as well as limit further downstream release of cytochrome c and cleavage of caspases 8 and 3; we suggest that TM interacts with the cofilin cytoskeleton, which further supports a role for TM in eotaxin-induced THP-1 cell apoptosis. Based on clinical observation and in vitro study, we conclude that TM expression on monocytes is associated with their apoptosis. The above mechanisms may be relevant to clinical phenomena in which patients exhibiting more monocytic apoptosis are complicated by higher plasma levels of eotaxin-2 and lower TM expression on monocytes after CABG surgery.

AB - Cardiopulmonary bypass (CPB) induces cytokine production and causes postoperative monocytic inflammatory responses, which are associated with patient outcomes. In fact, monocytes regulate immunity through dynamic networks of survival and cellular apoptosis as well as thrombomodulin (TM)-associated differenciiation. Whether CPB affects the plasma level of eotaxin-2, a potent chemoattractant, or stimulates monocyte apoptosis among patients undergoing elective coronary artery bypass graft (CABG) surgery is also unknown. Thus, we aimed to investigate this subject and explored the feasible roles of TM in the phenomena. Firstly, clinical data showed that after CABG surgery, patients with lower plasma eotaxin-2 levels and higher TM expression levels exhibited reduced monocytic apoptosis, compared with that in patients with lower TM expression levels. Subsequently, to explore the hypothesis that eotaxin-2 induces monocytic apoptosis mediation by TM expression, we used in vitro monocytic THP1 cells. The results indicated that treatment of THP-1 cells with eotaxin-2 markedly increased apoptosis. Knockdown of TM significantly increased, and overexpression of TM significantly reversed eotaxin-2-induced monocyte apoptosis, which was compared with that of only eotaxin-2-treated THP-1 cells. TM may regulate mitochondria-mediated apoptosis by its PI3K/Akt axis signaling pathway, which acts as an extinguisher for p53 and BAX activation, as well as limit further downstream release of cytochrome c and cleavage of caspases 8 and 3; we suggest that TM interacts with the cofilin cytoskeleton, which further supports a role for TM in eotaxin-induced THP-1 cell apoptosis. Based on clinical observation and in vitro study, we conclude that TM expression on monocytes is associated with their apoptosis. The above mechanisms may be relevant to clinical phenomena in which patients exhibiting more monocytic apoptosis are complicated by higher plasma levels of eotaxin-2 and lower TM expression on monocytes after CABG surgery.

KW - Apoptosis

KW - Eotaxin-2

KW - Thrombomodulin

UR - http://www.scopus.com/inward/record.url?scp=85056171123&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056171123&partnerID=8YFLogxK

M3 - Article

VL - 10

SP - 3133

EP - 3149

JO - American Journal of Translational Research

JF - American Journal of Translational Research

SN - 1943-8141

IS - 10

M1 - AJTR0081221

ER -