Mevastatin suppresses lipopolysaccharide-induced Rac activation in the human monocyte cell line THP-1

Tushar R. Patel, Siobhan A. Corbett

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background. Rac is a member of the Rho family of small guanosine triphosphatases that regulate the actin cytoskeleton. Activation of Rac requires lipid modification that can be blocked by statins. Lipopolysaccharide-induced rearrangements in the actin cytoskeleton lead to changes in cell adhesion and motility that play a role in the cellular response to infection. The lipid products of phosphatidylinositol-3 kinase (PI3K) modulate Rac effector pathways and have been linked to the activation of the Rac-guanosine triphosphatase. We hypothesize that lipopolysaccharide stimulation leads to Rac activation and that this may be inhibited by statin pretreatment. Furthermore, signaling downstream of Rac is linked to PI3K; therefore, we hypothesize that a signaling complex between PI3K and Rac may be involved. Methods. THP-1 cells were maintained in 1% fetal calf serum with or without 20 μmol/L mevastatin for 24 hours, followed by lipopolysaccharide stimulation. Active Rac was precipitated from THP-1 total cell lysate and then detected by immunoblotting. The PI3K-Rac complex was immunoprecipitated from total cell lysate, and the p85 regulatory subunit of P13K was detected by immunoblotting. Results. Lipopolysaccharide stimulation activated Rac. Rac activation was suppressed by pretreatment with mevastatin. The p85 subunit of PI3K was associated with Rac. Conclusion. Lipopolysaccharide stimulation leads to Rac activation in THP-1 cells, which may be suppressed with mevastatin pretreatment. There is an association between Rac and PI3K that demonstrates a role for PI3K in the activation of downstream Rac effector pathways.

Original languageEnglish (US)
Pages (from-to)306-311
Number of pages6
JournalSurgery
Volume134
Issue number2
DOIs
StatePublished - Aug 1 2003

Fingerprint

Phosphatidylinositol 3-Kinase
Lipopolysaccharides
Monocytes
Cell Line
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Guanosine
Actin Cytoskeleton
Immunoblotting
Lipids
mevastatin
Cell Adhesion
Cell Movement
Infection
Serum

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

@article{11d19d0f284d49d7b62aa7a5edc274fb,
title = "Mevastatin suppresses lipopolysaccharide-induced Rac activation in the human monocyte cell line THP-1",
abstract = "Background. Rac is a member of the Rho family of small guanosine triphosphatases that regulate the actin cytoskeleton. Activation of Rac requires lipid modification that can be blocked by statins. Lipopolysaccharide-induced rearrangements in the actin cytoskeleton lead to changes in cell adhesion and motility that play a role in the cellular response to infection. The lipid products of phosphatidylinositol-3 kinase (PI3K) modulate Rac effector pathways and have been linked to the activation of the Rac-guanosine triphosphatase. We hypothesize that lipopolysaccharide stimulation leads to Rac activation and that this may be inhibited by statin pretreatment. Furthermore, signaling downstream of Rac is linked to PI3K; therefore, we hypothesize that a signaling complex between PI3K and Rac may be involved. Methods. THP-1 cells were maintained in 1{\%} fetal calf serum with or without 20 μmol/L mevastatin for 24 hours, followed by lipopolysaccharide stimulation. Active Rac was precipitated from THP-1 total cell lysate and then detected by immunoblotting. The PI3K-Rac complex was immunoprecipitated from total cell lysate, and the p85 regulatory subunit of P13K was detected by immunoblotting. Results. Lipopolysaccharide stimulation activated Rac. Rac activation was suppressed by pretreatment with mevastatin. The p85 subunit of PI3K was associated with Rac. Conclusion. Lipopolysaccharide stimulation leads to Rac activation in THP-1 cells, which may be suppressed with mevastatin pretreatment. There is an association between Rac and PI3K that demonstrates a role for PI3K in the activation of downstream Rac effector pathways.",
author = "Patel, {Tushar R.} and Corbett, {Siobhan A.}",
year = "2003",
month = "8",
day = "1",
doi = "10.1067/msy.2003.241",
language = "English (US)",
volume = "134",
pages = "306--311",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "2",

}

Mevastatin suppresses lipopolysaccharide-induced Rac activation in the human monocyte cell line THP-1. / Patel, Tushar R.; Corbett, Siobhan A.

In: Surgery, Vol. 134, No. 2, 01.08.2003, p. 306-311.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mevastatin suppresses lipopolysaccharide-induced Rac activation in the human monocyte cell line THP-1

AU - Patel, Tushar R.

AU - Corbett, Siobhan A.

PY - 2003/8/1

Y1 - 2003/8/1

N2 - Background. Rac is a member of the Rho family of small guanosine triphosphatases that regulate the actin cytoskeleton. Activation of Rac requires lipid modification that can be blocked by statins. Lipopolysaccharide-induced rearrangements in the actin cytoskeleton lead to changes in cell adhesion and motility that play a role in the cellular response to infection. The lipid products of phosphatidylinositol-3 kinase (PI3K) modulate Rac effector pathways and have been linked to the activation of the Rac-guanosine triphosphatase. We hypothesize that lipopolysaccharide stimulation leads to Rac activation and that this may be inhibited by statin pretreatment. Furthermore, signaling downstream of Rac is linked to PI3K; therefore, we hypothesize that a signaling complex between PI3K and Rac may be involved. Methods. THP-1 cells were maintained in 1% fetal calf serum with or without 20 μmol/L mevastatin for 24 hours, followed by lipopolysaccharide stimulation. Active Rac was precipitated from THP-1 total cell lysate and then detected by immunoblotting. The PI3K-Rac complex was immunoprecipitated from total cell lysate, and the p85 regulatory subunit of P13K was detected by immunoblotting. Results. Lipopolysaccharide stimulation activated Rac. Rac activation was suppressed by pretreatment with mevastatin. The p85 subunit of PI3K was associated with Rac. Conclusion. Lipopolysaccharide stimulation leads to Rac activation in THP-1 cells, which may be suppressed with mevastatin pretreatment. There is an association between Rac and PI3K that demonstrates a role for PI3K in the activation of downstream Rac effector pathways.

AB - Background. Rac is a member of the Rho family of small guanosine triphosphatases that regulate the actin cytoskeleton. Activation of Rac requires lipid modification that can be blocked by statins. Lipopolysaccharide-induced rearrangements in the actin cytoskeleton lead to changes in cell adhesion and motility that play a role in the cellular response to infection. The lipid products of phosphatidylinositol-3 kinase (PI3K) modulate Rac effector pathways and have been linked to the activation of the Rac-guanosine triphosphatase. We hypothesize that lipopolysaccharide stimulation leads to Rac activation and that this may be inhibited by statin pretreatment. Furthermore, signaling downstream of Rac is linked to PI3K; therefore, we hypothesize that a signaling complex between PI3K and Rac may be involved. Methods. THP-1 cells were maintained in 1% fetal calf serum with or without 20 μmol/L mevastatin for 24 hours, followed by lipopolysaccharide stimulation. Active Rac was precipitated from THP-1 total cell lysate and then detected by immunoblotting. The PI3K-Rac complex was immunoprecipitated from total cell lysate, and the p85 regulatory subunit of P13K was detected by immunoblotting. Results. Lipopolysaccharide stimulation activated Rac. Rac activation was suppressed by pretreatment with mevastatin. The p85 subunit of PI3K was associated with Rac. Conclusion. Lipopolysaccharide stimulation leads to Rac activation in THP-1 cells, which may be suppressed with mevastatin pretreatment. There is an association between Rac and PI3K that demonstrates a role for PI3K in the activation of downstream Rac effector pathways.

UR - http://www.scopus.com/inward/record.url?scp=0042328042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042328042&partnerID=8YFLogxK

U2 - 10.1067/msy.2003.241

DO - 10.1067/msy.2003.241

M3 - Article

C2 - 12947334

AN - SCOPUS:0042328042

VL - 134

SP - 306

EP - 311

JO - Surgery

JF - Surgery

SN - 0039-6060

IS - 2

ER -