Abstract

Background: Hypertonic stress enhances tumor necrosis factor (TNF)-α expression in activated monocytes. However, the underlying mechanism is unknown. The produced TNF-α is primarily cleaved and released by TNF-α-converting enzyme (TACE), and the surface expression of TACE is down-regulated by endocytosis. As hypertonicity inhibits endocytosis, we evaluated the mechanism of hypertonicity-induced TNF-α release from activated human monocytic THP-1 cells. Methods: THP-1 cells were stimulated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) in the presence or absence of hypertonic agents (150 mM sucrose or 150-300 mM NaCl). The amount of TNF-α mRNA and protein, surface expression of TACE and activation of signaling pathways (mitogen-activated protein kinase, Akt and NF-κB) were assayed. Results: Hypertonic sucrose and NaCl significantly enhanced TNF-α release from THP-1 cells upon LPS or PMA stimulation. Hypertonic sucrose and other endocytosis inhibitors increased surface expression of TACE, but their effects on TNF-α release were inconsistent. This enhancement effect by hypertonicity was not attenuated by inhibition of TACE or IκB kinase, but it was blocked by cycloheximide and a MAP/ERK kinase inhibitor. The LPS- or PMA-induced TNF-α mRNA expression was not increased; rather, it was inhibited by hypertonicity. ERK1/2 was re-activated after sucrose treatment in LPS-stimulated THP-1 cells. Conclusions: Hypertonicity-enhanced TNF-α protein synthesis from LPS- or PMA-activated THP-1 cells requires ERK activation and may proceed without TACE. General significance: A vast amount of TNF-α production was regulated by a crucial post-transcriptional manner in activated human monocytic leukemia cells, and it may possibly be contributed to the cachexia condition.

Original languageEnglish
Pages (from-to)475-484
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1810
Issue number4
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Tumor Necrosis Factor-alpha
Chemical activation
Lipopolysaccharides
Sucrose
Acetates
Endocytosis
Messenger RNA
Cachexia
Mitogen-Activated Protein Kinase Kinases
Osmotic Pressure
Cycloheximide
Mitogen-Activated Protein Kinases
Monocytes
Membrane Proteins
Leukemia
Phosphotransferases
phorbol-12-myristate
Enzymes
Proteins

Keywords

  • Endocytosis
  • Hypertonicity
  • LPS
  • PMA
  • TACE
  • TNF-α

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Hypertonicity-enhanced TNF-α release from activated human monocytic THP-1 cells requires ERK activation. / Chou, Yung Chen; Sheu, Joen Rong; Chung, Chi Li; Hsiao, Che Jen; Hsueh, Po Jen; Hsiao, George.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1810, No. 4, 04.2011, p. 475-484.

Research output: Contribution to journalArticle

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abstract = "Background: Hypertonic stress enhances tumor necrosis factor (TNF)-α expression in activated monocytes. However, the underlying mechanism is unknown. The produced TNF-α is primarily cleaved and released by TNF-α-converting enzyme (TACE), and the surface expression of TACE is down-regulated by endocytosis. As hypertonicity inhibits endocytosis, we evaluated the mechanism of hypertonicity-induced TNF-α release from activated human monocytic THP-1 cells. Methods: THP-1 cells were stimulated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) in the presence or absence of hypertonic agents (150 mM sucrose or 150-300 mM NaCl). The amount of TNF-α mRNA and protein, surface expression of TACE and activation of signaling pathways (mitogen-activated protein kinase, Akt and NF-κB) were assayed. Results: Hypertonic sucrose and NaCl significantly enhanced TNF-α release from THP-1 cells upon LPS or PMA stimulation. Hypertonic sucrose and other endocytosis inhibitors increased surface expression of TACE, but their effects on TNF-α release were inconsistent. This enhancement effect by hypertonicity was not attenuated by inhibition of TACE or IκB kinase, but it was blocked by cycloheximide and a MAP/ERK kinase inhibitor. The LPS- or PMA-induced TNF-α mRNA expression was not increased; rather, it was inhibited by hypertonicity. ERK1/2 was re-activated after sucrose treatment in LPS-stimulated THP-1 cells. Conclusions: Hypertonicity-enhanced TNF-α protein synthesis from LPS- or PMA-activated THP-1 cells requires ERK activation and may proceed without TACE. General significance: A vast amount of TNF-α production was regulated by a crucial post-transcriptional manner in activated human monocytic leukemia cells, and it may possibly be contributed to the cachexia condition.",
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author = "Chou, {Yung Chen} and Sheu, {Joen Rong} and Chung, {Chi Li} and Hsiao, {Che Jen} and Hsueh, {Po Jen} and George Hsiao",
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T1 - Hypertonicity-enhanced TNF-α release from activated human monocytic THP-1 cells requires ERK activation

AU - Chou, Yung Chen

AU - Sheu, Joen Rong

AU - Chung, Chi Li

AU - Hsiao, Che Jen

AU - Hsueh, Po Jen

AU - Hsiao, George

PY - 2011/4

Y1 - 2011/4

N2 - Background: Hypertonic stress enhances tumor necrosis factor (TNF)-α expression in activated monocytes. However, the underlying mechanism is unknown. The produced TNF-α is primarily cleaved and released by TNF-α-converting enzyme (TACE), and the surface expression of TACE is down-regulated by endocytosis. As hypertonicity inhibits endocytosis, we evaluated the mechanism of hypertonicity-induced TNF-α release from activated human monocytic THP-1 cells. Methods: THP-1 cells were stimulated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) in the presence or absence of hypertonic agents (150 mM sucrose or 150-300 mM NaCl). The amount of TNF-α mRNA and protein, surface expression of TACE and activation of signaling pathways (mitogen-activated protein kinase, Akt and NF-κB) were assayed. Results: Hypertonic sucrose and NaCl significantly enhanced TNF-α release from THP-1 cells upon LPS or PMA stimulation. Hypertonic sucrose and other endocytosis inhibitors increased surface expression of TACE, but their effects on TNF-α release were inconsistent. This enhancement effect by hypertonicity was not attenuated by inhibition of TACE or IκB kinase, but it was blocked by cycloheximide and a MAP/ERK kinase inhibitor. The LPS- or PMA-induced TNF-α mRNA expression was not increased; rather, it was inhibited by hypertonicity. ERK1/2 was re-activated after sucrose treatment in LPS-stimulated THP-1 cells. Conclusions: Hypertonicity-enhanced TNF-α protein synthesis from LPS- or PMA-activated THP-1 cells requires ERK activation and may proceed without TACE. General significance: A vast amount of TNF-α production was regulated by a crucial post-transcriptional manner in activated human monocytic leukemia cells, and it may possibly be contributed to the cachexia condition.

AB - Background: Hypertonic stress enhances tumor necrosis factor (TNF)-α expression in activated monocytes. However, the underlying mechanism is unknown. The produced TNF-α is primarily cleaved and released by TNF-α-converting enzyme (TACE), and the surface expression of TACE is down-regulated by endocytosis. As hypertonicity inhibits endocytosis, we evaluated the mechanism of hypertonicity-induced TNF-α release from activated human monocytic THP-1 cells. Methods: THP-1 cells were stimulated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) in the presence or absence of hypertonic agents (150 mM sucrose or 150-300 mM NaCl). The amount of TNF-α mRNA and protein, surface expression of TACE and activation of signaling pathways (mitogen-activated protein kinase, Akt and NF-κB) were assayed. Results: Hypertonic sucrose and NaCl significantly enhanced TNF-α release from THP-1 cells upon LPS or PMA stimulation. Hypertonic sucrose and other endocytosis inhibitors increased surface expression of TACE, but their effects on TNF-α release were inconsistent. This enhancement effect by hypertonicity was not attenuated by inhibition of TACE or IκB kinase, but it was blocked by cycloheximide and a MAP/ERK kinase inhibitor. The LPS- or PMA-induced TNF-α mRNA expression was not increased; rather, it was inhibited by hypertonicity. ERK1/2 was re-activated after sucrose treatment in LPS-stimulated THP-1 cells. Conclusions: Hypertonicity-enhanced TNF-α protein synthesis from LPS- or PMA-activated THP-1 cells requires ERK activation and may proceed without TACE. General significance: A vast amount of TNF-α production was regulated by a crucial post-transcriptional manner in activated human monocytic leukemia cells, and it may possibly be contributed to the cachexia condition.

KW - Endocytosis

KW - Hypertonicity

KW - LPS

KW - PMA

KW - TACE

KW - TNF-α

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