Propofol significantly attenuates iNOS, CAT-2, and CAT-2B transcription in lipopolysaccharide-stimulated murine macrophages

Meng Chi Liu, Pei Shan Tsai, Chen Hsien Yang, Cheng Hung Liu, Chien Chuan Chen, Chun Jen Huang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Propofol significantly inhibits inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) biosynthesis in stimulated macrophages. L-arginine transport mediated by the isozymes of type-2 cationic amino acid transporter (including CAT-2 and CAT-2B) has been reported to play a crucial role in regulating iNOS activity. We sought to evaluate the effects of propofol on L-arginine transport and transcription of CAT-2 and CAT-2B. Methods: Confluent murine macrophages (RAW264.7 cells) were stimulated with lipopolysaccharide (LPS) to induce NO production, L-arginine transport and the transcriptions of iNOS, CAT-2, and CAT-2B. Propofol (25, 50, and 75 μM) was added to the cells 4 hours before, immediately after, or 4 hours after LPS administration. After reacting with LPS for 18 hours, cell cultures were harvested and assayed. Results: Propofol administered 4 hours before LPS had no significant effects on NO production, L-arginine transport, and the transcriptions of iNOS and CAT-2. To our surprise, NO production and iNOS transcription were significantly enhanced by 25 μM propofol administered immediately after LPS. NO production and iNOS transcription were not affected by 50 μM propofol but significantly inhibited by 75 μM propofol administered immediately after LPS. CAT-2 transcription and L-arginine transport were significantly inhibited by 50 and 75 μM but not 25 μM propofol administered immediately after LPS. When administered 4 hours after LPS, 75 but not 25 and 50 μM propofol significantly inhibited NO production, L-arginine transport, and the transcription of iNOS and CAT-2. In addition, CAT-2B transcription was significantly inhibited by propofol that was administered 4 hours before, immediately after, or 4 hours after LPS. Conclusions: Propofol had significantly inhibitory effects on LPS-induced NO production, L-arginine transport, and the expressions of iNOS, CAT-2 and CAT-2B in stimulated murine macrophages in a dose-dependent manner. In addition, timing of administration also affected this regulatory effect of propofol.

Original languageEnglish
Pages (from-to)73-81
Number of pages9
JournalActa Anaesthesiologica Taiwanica
Volume44
Issue number2
Publication statusPublished - Jun 2006

Fingerprint

Propofol
Nitric Oxide Synthase Type II
Lipopolysaccharides
Macrophages
Arginine
Nitric Oxide
Cationic Amino Acid Transporter 2
Isoenzymes
Cell Culture Techniques

Keywords

  • Cationic amino acid transporter 2
  • Lipopolysaccharides
  • Macrophage
  • Nitric oxide synthase
  • Propofol

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Propofol significantly attenuates iNOS, CAT-2, and CAT-2B transcription in lipopolysaccharide-stimulated murine macrophages. / Liu, Meng Chi; Tsai, Pei Shan; Yang, Chen Hsien; Liu, Cheng Hung; Chen, Chien Chuan; Huang, Chun Jen.

In: Acta Anaesthesiologica Taiwanica, Vol. 44, No. 2, 06.2006, p. 73-81.

Research output: Contribution to journalArticle

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abstract = "Background: Propofol significantly inhibits inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) biosynthesis in stimulated macrophages. L-arginine transport mediated by the isozymes of type-2 cationic amino acid transporter (including CAT-2 and CAT-2B) has been reported to play a crucial role in regulating iNOS activity. We sought to evaluate the effects of propofol on L-arginine transport and transcription of CAT-2 and CAT-2B. Methods: Confluent murine macrophages (RAW264.7 cells) were stimulated with lipopolysaccharide (LPS) to induce NO production, L-arginine transport and the transcriptions of iNOS, CAT-2, and CAT-2B. Propofol (25, 50, and 75 μM) was added to the cells 4 hours before, immediately after, or 4 hours after LPS administration. After reacting with LPS for 18 hours, cell cultures were harvested and assayed. Results: Propofol administered 4 hours before LPS had no significant effects on NO production, L-arginine transport, and the transcriptions of iNOS and CAT-2. To our surprise, NO production and iNOS transcription were significantly enhanced by 25 μM propofol administered immediately after LPS. NO production and iNOS transcription were not affected by 50 μM propofol but significantly inhibited by 75 μM propofol administered immediately after LPS. CAT-2 transcription and L-arginine transport were significantly inhibited by 50 and 75 μM but not 25 μM propofol administered immediately after LPS. When administered 4 hours after LPS, 75 but not 25 and 50 μM propofol significantly inhibited NO production, L-arginine transport, and the transcription of iNOS and CAT-2. In addition, CAT-2B transcription was significantly inhibited by propofol that was administered 4 hours before, immediately after, or 4 hours after LPS. Conclusions: Propofol had significantly inhibitory effects on LPS-induced NO production, L-arginine transport, and the expressions of iNOS, CAT-2 and CAT-2B in stimulated murine macrophages in a dose-dependent manner. In addition, timing of administration also affected this regulatory effect of propofol.",
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author = "Liu, {Meng Chi} and Tsai, {Pei Shan} and Yang, {Chen Hsien} and Liu, {Cheng Hung} and Chen, {Chien Chuan} and Huang, {Chun Jen}",
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T1 - Propofol significantly attenuates iNOS, CAT-2, and CAT-2B transcription in lipopolysaccharide-stimulated murine macrophages

AU - Liu, Meng Chi

AU - Tsai, Pei Shan

AU - Yang, Chen Hsien

AU - Liu, Cheng Hung

AU - Chen, Chien Chuan

AU - Huang, Chun Jen

PY - 2006/6

Y1 - 2006/6

N2 - Background: Propofol significantly inhibits inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) biosynthesis in stimulated macrophages. L-arginine transport mediated by the isozymes of type-2 cationic amino acid transporter (including CAT-2 and CAT-2B) has been reported to play a crucial role in regulating iNOS activity. We sought to evaluate the effects of propofol on L-arginine transport and transcription of CAT-2 and CAT-2B. Methods: Confluent murine macrophages (RAW264.7 cells) were stimulated with lipopolysaccharide (LPS) to induce NO production, L-arginine transport and the transcriptions of iNOS, CAT-2, and CAT-2B. Propofol (25, 50, and 75 μM) was added to the cells 4 hours before, immediately after, or 4 hours after LPS administration. After reacting with LPS for 18 hours, cell cultures were harvested and assayed. Results: Propofol administered 4 hours before LPS had no significant effects on NO production, L-arginine transport, and the transcriptions of iNOS and CAT-2. To our surprise, NO production and iNOS transcription were significantly enhanced by 25 μM propofol administered immediately after LPS. NO production and iNOS transcription were not affected by 50 μM propofol but significantly inhibited by 75 μM propofol administered immediately after LPS. CAT-2 transcription and L-arginine transport were significantly inhibited by 50 and 75 μM but not 25 μM propofol administered immediately after LPS. When administered 4 hours after LPS, 75 but not 25 and 50 μM propofol significantly inhibited NO production, L-arginine transport, and the transcription of iNOS and CAT-2. In addition, CAT-2B transcription was significantly inhibited by propofol that was administered 4 hours before, immediately after, or 4 hours after LPS. Conclusions: Propofol had significantly inhibitory effects on LPS-induced NO production, L-arginine transport, and the expressions of iNOS, CAT-2 and CAT-2B in stimulated murine macrophages in a dose-dependent manner. In addition, timing of administration also affected this regulatory effect of propofol.

AB - Background: Propofol significantly inhibits inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) biosynthesis in stimulated macrophages. L-arginine transport mediated by the isozymes of type-2 cationic amino acid transporter (including CAT-2 and CAT-2B) has been reported to play a crucial role in regulating iNOS activity. We sought to evaluate the effects of propofol on L-arginine transport and transcription of CAT-2 and CAT-2B. Methods: Confluent murine macrophages (RAW264.7 cells) were stimulated with lipopolysaccharide (LPS) to induce NO production, L-arginine transport and the transcriptions of iNOS, CAT-2, and CAT-2B. Propofol (25, 50, and 75 μM) was added to the cells 4 hours before, immediately after, or 4 hours after LPS administration. After reacting with LPS for 18 hours, cell cultures were harvested and assayed. Results: Propofol administered 4 hours before LPS had no significant effects on NO production, L-arginine transport, and the transcriptions of iNOS and CAT-2. To our surprise, NO production and iNOS transcription were significantly enhanced by 25 μM propofol administered immediately after LPS. NO production and iNOS transcription were not affected by 50 μM propofol but significantly inhibited by 75 μM propofol administered immediately after LPS. CAT-2 transcription and L-arginine transport were significantly inhibited by 50 and 75 μM but not 25 μM propofol administered immediately after LPS. When administered 4 hours after LPS, 75 but not 25 and 50 μM propofol significantly inhibited NO production, L-arginine transport, and the transcription of iNOS and CAT-2. In addition, CAT-2B transcription was significantly inhibited by propofol that was administered 4 hours before, immediately after, or 4 hours after LPS. Conclusions: Propofol had significantly inhibitory effects on LPS-induced NO production, L-arginine transport, and the expressions of iNOS, CAT-2 and CAT-2B in stimulated murine macrophages in a dose-dependent manner. In addition, timing of administration also affected this regulatory effect of propofol.

KW - Cationic amino acid transporter 2

KW - Lipopolysaccharides

KW - Macrophage

KW - Nitric oxide synthase

KW - Propofol

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