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Geranylgeranylacetone ameliorates inflammatory response to lipopolysaccharide (LPS) in murine macrophages: inhibition of LPS binding to the cell surface.

Mochida S, Matsura T, Yamashita A, Horie S, Ohata S, Kusumoto C, Nishida T, Minami Y, Inagaki Y, Ishibe Y, Nakada J, Ohta Y, Yamada K - J Clin Biochem Nutr (2007)

Bottom Line: GGA (80 microM) treatment 2 h before LPS addition significantly suppressed TNF-alpha and NO productions at 12 h and 24 h after LPS, respectively, indicating that GGA inhibits activation of macrophages.When it was examined whether GGA interacts with LPS and/or affects expression of Toll-like receptor 4 (TLR4) and CD14 on the cell surface, GGA inhibited the binding of LPS to the cell surface, while GGA did not affect TLR4 and CD14 expressions.These results indicate that GGA suppresses the binding of LPS to the cell surface of macrophages, resulting in inhibiting signal transduction downstream of TLR4.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, 86 Nishi-cho, Yonago 683-8503, Japan.

ABSTRACT
We investigated whether pretreatment with geranylgeranylacetone (GGA), a potent heat shock protein (HSP) inducer, could inhibit proinflammatory cytokine liberation and nitric oxide (NO) production in lipopolysaccharide (LPS)-treated murine macrophages. The levels of NO and tumor necrosis factor-alpha (TNF-alpha) released from murine macrophage RAW 264 cells were increased dose- and time-dependently following treatment with LPS (1 microg/ml). GGA (80 microM) treatment 2 h before LPS addition significantly suppressed TNF-alpha and NO productions at 12 h and 24 h after LPS, respectively, indicating that GGA inhibits activation of macrophages. However, replacement by fresh culture medium before LPS treatment abolished the inhibitory effect of GGA on NO production in LPS-treated cells. Furthermore, GGA inhibited both HSP70 and inducible NO synthase expressions induced by LPS treatment despite an HSP inducer. When it was examined whether GGA interacts with LPS and/or affects expression of Toll-like receptor 4 (TLR4) and CD14 on the cell surface, GGA inhibited the binding of LPS to the cell surface, while GGA did not affect TLR4 and CD14 expressions. These results indicate that GGA suppresses the binding of LPS to the cell surface of macrophages, resulting in inhibiting signal transduction downstream of TLR4.

No MeSH data available.


Related in: MedlinePlus

Effect of replacement by fresh culture medium before LPS administration on inhibition by GGA of NO production in LPS-treated RAW 264 cells. GGA (0, 20, 40, or 80 µM) was added to the medium 2 h before LPS administration and subsequently culture medium was replaced by fresh one without GGA just before LPS addition. Cells were further incubated in the presence of LPS (1 µg/ml) for 24 h at 37°C under a 5% CO2 and 95% air atmosphere. The level of NO in the medium was measured as described in Materials and Methods. Data points represent the means ± SE (n = 3).
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Figure 6: Effect of replacement by fresh culture medium before LPS administration on inhibition by GGA of NO production in LPS-treated RAW 264 cells. GGA (0, 20, 40, or 80 µM) was added to the medium 2 h before LPS administration and subsequently culture medium was replaced by fresh one without GGA just before LPS addition. Cells were further incubated in the presence of LPS (1 µg/ml) for 24 h at 37°C under a 5% CO2 and 95% air atmosphere. The level of NO in the medium was measured as described in Materials and Methods. Data points represent the means ± SE (n = 3).

Mentions: When GGA (20, 40 or 80 µM) was added to the medium 2 h before LPS administration and subsequently culture medium was replaced by fresh one without GGA just before LPS addition, the inhibitory effect of GGA on NO production induced by LPS in the cells was abolished (Fig. 6).


Geranylgeranylacetone ameliorates inflammatory response to lipopolysaccharide (LPS) in murine macrophages: inhibition of LPS binding to the cell surface.

Mochida S, Matsura T, Yamashita A, Horie S, Ohata S, Kusumoto C, Nishida T, Minami Y, Inagaki Y, Ishibe Y, Nakada J, Ohta Y, Yamada K - J Clin Biochem Nutr (2007)

Effect of replacement by fresh culture medium before LPS administration on inhibition by GGA of NO production in LPS-treated RAW 264 cells. GGA (0, 20, 40, or 80 µM) was added to the medium 2 h before LPS administration and subsequently culture medium was replaced by fresh one without GGA just before LPS addition. Cells were further incubated in the presence of LPS (1 µg/ml) for 24 h at 37°C under a 5% CO2 and 95% air atmosphere. The level of NO in the medium was measured as described in Materials and Methods. Data points represent the means ± SE (n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 6: Effect of replacement by fresh culture medium before LPS administration on inhibition by GGA of NO production in LPS-treated RAW 264 cells. GGA (0, 20, 40, or 80 µM) was added to the medium 2 h before LPS administration and subsequently culture medium was replaced by fresh one without GGA just before LPS addition. Cells were further incubated in the presence of LPS (1 µg/ml) for 24 h at 37°C under a 5% CO2 and 95% air atmosphere. The level of NO in the medium was measured as described in Materials and Methods. Data points represent the means ± SE (n = 3).
Mentions: When GGA (20, 40 or 80 µM) was added to the medium 2 h before LPS administration and subsequently culture medium was replaced by fresh one without GGA just before LPS addition, the inhibitory effect of GGA on NO production induced by LPS in the cells was abolished (Fig. 6).

Bottom Line: GGA (80 microM) treatment 2 h before LPS addition significantly suppressed TNF-alpha and NO productions at 12 h and 24 h after LPS, respectively, indicating that GGA inhibits activation of macrophages.When it was examined whether GGA interacts with LPS and/or affects expression of Toll-like receptor 4 (TLR4) and CD14 on the cell surface, GGA inhibited the binding of LPS to the cell surface, while GGA did not affect TLR4 and CD14 expressions.These results indicate that GGA suppresses the binding of LPS to the cell surface of macrophages, resulting in inhibiting signal transduction downstream of TLR4.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, 86 Nishi-cho, Yonago 683-8503, Japan.

ABSTRACT
We investigated whether pretreatment with geranylgeranylacetone (GGA), a potent heat shock protein (HSP) inducer, could inhibit proinflammatory cytokine liberation and nitric oxide (NO) production in lipopolysaccharide (LPS)-treated murine macrophages. The levels of NO and tumor necrosis factor-alpha (TNF-alpha) released from murine macrophage RAW 264 cells were increased dose- and time-dependently following treatment with LPS (1 microg/ml). GGA (80 microM) treatment 2 h before LPS addition significantly suppressed TNF-alpha and NO productions at 12 h and 24 h after LPS, respectively, indicating that GGA inhibits activation of macrophages. However, replacement by fresh culture medium before LPS treatment abolished the inhibitory effect of GGA on NO production in LPS-treated cells. Furthermore, GGA inhibited both HSP70 and inducible NO synthase expressions induced by LPS treatment despite an HSP inducer. When it was examined whether GGA interacts with LPS and/or affects expression of Toll-like receptor 4 (TLR4) and CD14 on the cell surface, GGA inhibited the binding of LPS to the cell surface, while GGA did not affect TLR4 and CD14 expressions. These results indicate that GGA suppresses the binding of LPS to the cell surface of macrophages, resulting in inhibiting signal transduction downstream of TLR4.

No MeSH data available.


Related in: MedlinePlus