References
Query Results -- Details
MGI Accession ID: MGI:3765395
J Number: J:128040
Other Accession IDs:
Title: Regulation of cyclooxygenase-2 expression by small GTPase Rac2 in bone marrow macrophages.
Authors: Azim AC; Cao H; Gao X; Joo M; Malik AB; van Breemen RB; Sadikot RT; Park G; Christman JW
Journal: Am J Physiol Lung Cell Mol Physiol
Volume: 293
Issue: 3
Date: 2007 Sep
Year: 2007
Pages: L668-73
Review Status: Peer Reviewed
Abstract:
Cyclooxygenase 2 (COX-2) is induced by microbial products, proinflammatory cytokines, growth factors, and oncogenes. The Rho family includes RhoA, Rac1, Rac2, Rac3, and Cdc42 and is involved in regulation of the actin cytoskeleton organization, cell growth, vesicular cell trafficking, and transcriptional regulation. Rac2 binds to NADPH oxidase protein complex, and Rac2 null neutrophils are known to have poor phagocytic activity. We examined whether Rac2, the predominant small GTPase in hematopoietic cells, influences COX-2 expression in bone marrow-derived macrophages (BMDM). We showed that BMDM from Rac2(-/-) null mice have reduced COX-2 expression in response to treatment with endotoxin. Despite a compensatory increase in Rac1, BMDM from Rac2(-/-) null mice have less biologically active GTP-bound Rac in response to LPS stimulation. Signaling molecules (downstream of Rac2 and Toll-like receptor 4) such as p42/44, p38, and pAKT were also affected in BMDM from Rac2(-/-) null mouse macrophages. We also observed that BMDM from Rac2(-/-) null failed to degrade IkappaBalpha significantly and had less immunoreactive PU.1. We show that both NF-kappaB pathway and PU.1 are involved in normal macrophage function and play a role in macrophage COX-2 expression. In summary, these data indicate that Rac2 regulates COX-2 expression in BMDM.
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