Ginkgo biloba extract suppresses endotoxin-mediated monocyte activation by inhibiting nitric oxide- and tristetraprolin-mediated toll-like receptor 4 expression

Yuan-Wen Lee, Jui-An Lin, Chuen-Chau Chang, Yung Hsiang Chen, Po Len Liu, Ai-Wei Lee, Jui Chi Tsai, Chi Yuan Li, Chien Sung Tsai, Ta-Liang Chen, Feng-Yen Lin

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12 Citations (Scopus)

Abstract

Monocytes expressing toll-like receptor 4 (TLR4) play a major role in regulating the innate immune response and are involved in systemic inflammation. Previous studies have shown that Ginkgo biloba extract (GBE) may act as a therapeutic agent for some cardiovascular and neurological disorders. The objective of this study was to determine whether GBE could modulate immunity in human cells. The monocytic cell line THP-1 was used. Enzyme-linked immunosorbent assay results showed that lipopolysaccharide (LPS) induces the expression of monocyte chemotactic protein-1 (MIP-1), tumor necrosis factor-α, stromal cell-derived factor-1, and MIP-1α, and this induction may be repressed by GBE treatment due to TLR4 blockade. The Griess reagent assay and western blot analysis showed that GBE-mediated inhibition of TLR4 expression was associated with the activation of mitogen-activated protein kinase and production of nitric oxide (NO). Actinomycin D chase experiments demonstrated that GBE decreased the TLR4 mRNA stability in cells. Confocal microscopy and real-time polymerase chain reaction showed that GBE induced the expression of intracellular tristetraprolin (TTP). Transfection with TTP siRNA reversed the effects of GBE in naïve or TLR4-overexpressing cells. Treatment with SNAP (an NO donor) may increase intracellular TTP expression in cells. Immunoprecipitation analysis showed that GBE mediates TTP activation and increases the interaction of TTP with the 3' untranslated region (UTR) of TLR4 mRNA by regulating NO production. Our findings indicate that GBE could decrease the sensitivity of monocytes to LPS. Utilizing TTP to control TLR4 expression may be a promising approach for controlling systemic inflammation, and GBE may have potential applications in the clinical treatment of immune diseases.

Original languageEnglish
Pages (from-to)351-359
Number of pages9
JournalJournal of Nutritional Biochemistry
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Tristetraprolin
Ginkgo biloba
Toll-Like Receptor 4
Endotoxins
Monocytes
Nitric Oxide
Chemical activation
Chemokine CCL2
Lipopolysaccharides
Assays
Cells
Chemokine CXCL12
Cardiovascular Agents
Immunosorbents
Messenger RNA
Nitric Oxide Donors
Confocal microscopy
Polymerase chain reaction
3' Untranslated Regions
Dactinomycin

Keywords

  • Ginkgo biloba extract
  • Nitric oxide
  • Toll-like receptor 4
  • Tristetraprolin

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

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title = "Ginkgo biloba extract suppresses endotoxin-mediated monocyte activation by inhibiting nitric oxide- and tristetraprolin-mediated toll-like receptor 4 expression",
abstract = "Monocytes expressing toll-like receptor 4 (TLR4) play a major role in regulating the innate immune response and are involved in systemic inflammation. Previous studies have shown that Ginkgo biloba extract (GBE) may act as a therapeutic agent for some cardiovascular and neurological disorders. The objective of this study was to determine whether GBE could modulate immunity in human cells. The monocytic cell line THP-1 was used. Enzyme-linked immunosorbent assay results showed that lipopolysaccharide (LPS) induces the expression of monocyte chemotactic protein-1 (MIP-1), tumor necrosis factor-α, stromal cell-derived factor-1, and MIP-1α, and this induction may be repressed by GBE treatment due to TLR4 blockade. The Griess reagent assay and western blot analysis showed that GBE-mediated inhibition of TLR4 expression was associated with the activation of mitogen-activated protein kinase and production of nitric oxide (NO). Actinomycin D chase experiments demonstrated that GBE decreased the TLR4 mRNA stability in cells. Confocal microscopy and real-time polymerase chain reaction showed that GBE induced the expression of intracellular tristetraprolin (TTP). Transfection with TTP siRNA reversed the effects of GBE in na{\"i}ve or TLR4-overexpressing cells. Treatment with SNAP (an NO donor) may increase intracellular TTP expression in cells. Immunoprecipitation analysis showed that GBE mediates TTP activation and increases the interaction of TTP with the 3' untranslated region (UTR) of TLR4 mRNA by regulating NO production. Our findings indicate that GBE could decrease the sensitivity of monocytes to LPS. Utilizing TTP to control TLR4 expression may be a promising approach for controlling systemic inflammation, and GBE may have potential applications in the clinical treatment of immune diseases.",
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author = "Yuan-Wen Lee and Jui-An Lin and Chuen-Chau Chang and Chen, {Yung Hsiang} and Liu, {Po Len} and Ai-Wei Lee and Tsai, {Jui Chi} and Li, {Chi Yuan} and Tsai, {Chien Sung} and Ta-Liang Chen and Feng-Yen Lin",
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T1 - Ginkgo biloba extract suppresses endotoxin-mediated monocyte activation by inhibiting nitric oxide- and tristetraprolin-mediated toll-like receptor 4 expression

AU - Lee, Yuan-Wen

AU - Lin, Jui-An

AU - Chang, Chuen-Chau

AU - Chen, Yung Hsiang

AU - Liu, Po Len

AU - Lee, Ai-Wei

AU - Tsai, Jui Chi

AU - Li, Chi Yuan

AU - Tsai, Chien Sung

AU - Chen, Ta-Liang

AU - Lin, Feng-Yen

PY - 2011/4

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N2 - Monocytes expressing toll-like receptor 4 (TLR4) play a major role in regulating the innate immune response and are involved in systemic inflammation. Previous studies have shown that Ginkgo biloba extract (GBE) may act as a therapeutic agent for some cardiovascular and neurological disorders. The objective of this study was to determine whether GBE could modulate immunity in human cells. The monocytic cell line THP-1 was used. Enzyme-linked immunosorbent assay results showed that lipopolysaccharide (LPS) induces the expression of monocyte chemotactic protein-1 (MIP-1), tumor necrosis factor-α, stromal cell-derived factor-1, and MIP-1α, and this induction may be repressed by GBE treatment due to TLR4 blockade. The Griess reagent assay and western blot analysis showed that GBE-mediated inhibition of TLR4 expression was associated with the activation of mitogen-activated protein kinase and production of nitric oxide (NO). Actinomycin D chase experiments demonstrated that GBE decreased the TLR4 mRNA stability in cells. Confocal microscopy and real-time polymerase chain reaction showed that GBE induced the expression of intracellular tristetraprolin (TTP). Transfection with TTP siRNA reversed the effects of GBE in naïve or TLR4-overexpressing cells. Treatment with SNAP (an NO donor) may increase intracellular TTP expression in cells. Immunoprecipitation analysis showed that GBE mediates TTP activation and increases the interaction of TTP with the 3' untranslated region (UTR) of TLR4 mRNA by regulating NO production. Our findings indicate that GBE could decrease the sensitivity of monocytes to LPS. Utilizing TTP to control TLR4 expression may be a promising approach for controlling systemic inflammation, and GBE may have potential applications in the clinical treatment of immune diseases.

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