TNF-α inhibits toll-like receptor 4 expression on monocytic cells via tristetraprolin during cardiopulmonary bypass

Chien Sung Tsai, Da Liang Chen, Sing Jong Lin, Jui Chi Tsai, Tso Chou Lin, Chih Yuan Lin, Yung Hsiang Chen, Go Shine Huang, Hsiao Ya Tsai, Feng-Yen Lin, Chi Yuan Li

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Toll-like receptor 4 (TLR4) plays a major role in regulating the innate immune response, which is related to postoperative complications. Although inflammatory capacity and TNF-α synthesis were altered on monocytes after cardiopulmonary bypass (CPB), whether the CPB and the CPB-induced TNF-α affect TLR4 expression on monocytes have not yet clarified. We speculate that the changing of TNF-α level during CPB may be involved in monocytic TLR4 expression. As previous report, our enzyme-linked immunosorbent assay showed that CPB elevated the plasma level of TNF-α, whereas off-pump cardiac surgery does not. Flow cytometry reported decreased levels of monocytic TLR4 in patients undergoing CPB but not undergoing off-pump cardiac surgery. To elucidate whether the CPB-induced TNF-α is related to TLR4 down-regulation, we used human monocytic THP-1 cells. Actinomycin D chase experiments demonstrated that TNF-α decreased TLR4 expression and TLR4 mRNA stability on THP-1. Confocal microscopy and real-time polymerase chain reaction showed that TNF-α induced intracellular tristetraprolin (TTP) expression. Transfection with TTP siRNA reversed the down-regulation of TLR4 in TNF-α-stimulated THP-1. Treatment with ERK1/2 inhibitor and SAPK/JNK inhibitor decreased TNF-α-induced TTP expression. Immunoprecipitation and Western blot analysis showed that the TNF-α-mediated activation of TTP might be inhibited by p38 mitogen-activated protein kinase inhibitor and by PD98059. We also demonstrated in clinical samples with confocal microscopy and flow cytometry that CPB led to an elevation of TTP in monocytes. In conclusion, CPB and TNF-α decrease TLR4 expression on monocytes; TTP expression and mitogen-activated protein kinase-signaling pathways play critical roles in CPB- and TNF-α-mediated decreases of TLR4 on monocytes. Our results suggest that using TTP to control cytokine message decay rate may be a promising approach for controlling system inflammation and preventing post-CPB complications.

Original languageEnglish
Pages (from-to)40-48
Number of pages9
JournalShock
Volume32
Issue number1
DOIs
Publication statusPublished - Jul 2009

Fingerprint

Tristetraprolin
Toll-Like Receptor 4
Cardiopulmonary Bypass
Monocytes
Confocal Microscopy
Thoracic Surgery
Flow Cytometry
Down-Regulation
Critical Pathways
RNA Stability
Dactinomycin
p38 Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinases
Immunoprecipitation
Innate Immunity
Small Interfering RNA

Keywords

  • Cardiopulmonary bypass
  • Toll-like receptor
  • Tristetraprolin

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Tsai, C. S., Chen, D. L., Lin, S. J., Tsai, J. C., Lin, T. C., Lin, C. Y., ... Li, C. Y. (2009). TNF-α inhibits toll-like receptor 4 expression on monocytic cells via tristetraprolin during cardiopulmonary bypass. Shock, 32(1), 40-48. https://doi.org/10.1097/SHK.0b013e318199608d

TNF-α inhibits toll-like receptor 4 expression on monocytic cells via tristetraprolin during cardiopulmonary bypass. / Tsai, Chien Sung; Chen, Da Liang; Lin, Sing Jong; Tsai, Jui Chi; Lin, Tso Chou; Lin, Chih Yuan; Chen, Yung Hsiang; Huang, Go Shine; Tsai, Hsiao Ya; Lin, Feng-Yen; Li, Chi Yuan.

In: Shock, Vol. 32, No. 1, 07.2009, p. 40-48.

Research output: Contribution to journalArticle

Tsai, CS, Chen, DL, Lin, SJ, Tsai, JC, Lin, TC, Lin, CY, Chen, YH, Huang, GS, Tsai, HY, Lin, F-Y & Li, CY 2009, 'TNF-α inhibits toll-like receptor 4 expression on monocytic cells via tristetraprolin during cardiopulmonary bypass', Shock, vol. 32, no. 1, pp. 40-48. https://doi.org/10.1097/SHK.0b013e318199608d
Tsai, Chien Sung ; Chen, Da Liang ; Lin, Sing Jong ; Tsai, Jui Chi ; Lin, Tso Chou ; Lin, Chih Yuan ; Chen, Yung Hsiang ; Huang, Go Shine ; Tsai, Hsiao Ya ; Lin, Feng-Yen ; Li, Chi Yuan. / TNF-α inhibits toll-like receptor 4 expression on monocytic cells via tristetraprolin during cardiopulmonary bypass. In: Shock. 2009 ; Vol. 32, No. 1. pp. 40-48.
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