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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Article numberAJTR0081221
Pages (from-to)3133-3149
Number of pages17
JournalAmerican Journal of Translational Research
Volume10
Issue number10
Publication statusPublished - Jan 1 2018

Keywords

  • Apoptosis
  • Eotaxin-2
  • Thrombomodulin

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

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