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

Journal of Clinical Biochemistry and Nutrition
Shinsuke MochidaKazuo Yamada

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 ...Continue Reading

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Citations

Sep 28, 2012·Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology·Joanna HomaMagdalena Chadzinska
May 22, 2010·Journal of Clinical Biochemistry and Nutrition·Shuzo OhataTatsuya Matsura
Jun 12, 2008·Journal of Clinical Biochemistry and Nutrition·Gediminas Cepinskas, John X Wilson
Nov 1, 2011·Journal of Gastroenterology·Shigeyuki TakeshitaKazuhiko Nakao
Dec 5, 2008·Journal of Pineal Research·Eloisa GittoRussel J Reiter
May 12, 2011·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Salvatore AversaEloisa Gitto
Jun 15, 2017·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Fady M El-GendyMohamed G Hassan
Jul 1, 2020·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Seda KarabulutIlknur Keskin

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Methods Mentioned

BETA
FCS
enzyme-linked immunosorbent assay
Assay
electrophoresis
Protein Assay
flow cytometry

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