Journal article
A Phosphatidylcholine-Specific Phospholipase C Regulates Activation of p42/44 Mitogen-Activated Protein Kinases in Lipopolysaccharide-Stimulated Human Alveolar Macrophages
The Journal of immunology (1950), Vol.162(5), pp.3005-3012
03/01/1999
DOI: 10.4049/jimmunol.162.5.3005
PMID: 10072552
Abstract
Abstract This study uses human alveolar macrophages to determine whether activation of a phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) is linked to activation of the p42/44 (ERK) kinases by LPS. LPS-induced ERK kinase activation was inhibited by tricyclodecan-9-yl xanthogenate (D609), a relatively specific inhibitor of PC-PLC. LPS also increased amounts of diacylglycerol (DAG), and this increase in DAG was inhibited by D609. LPS induction of DAG was, at least in part, derived from PC hydrolysis. Ceramide was also increased in LPS-treated alveolar macrophages, and this increase in ceramide was inhibited by D609. Addition of exogenous C2 ceramide or bacterial-derived sphingomyelinase to alveolar macrophages increased ERK kinase activity. LPS also activated PKC ζ, and this activation was inhibited by D609. LPS-activated PKC ζ phosphorylated MAP kinase kinase, the kinase directly upstream of the ERK kinases. LPS-induced cytokine production (RNA and protein) was also inhibited by D609. As an aggregate, these studies support the hypothesis that one way by which LPS activates the ERK kinases is via activation of PC-PLC and that activation of a PC-PLC is an important component of macrophage activation by LPS.
Details
- Title: Subtitle
- A Phosphatidylcholine-Specific Phospholipase C Regulates Activation of p42/44 Mitogen-Activated Protein Kinases in Lipopolysaccharide-Stimulated Human Alveolar Macrophages
- Creators
- Martha M. Monick - University of IowaAaron Brent Carter - University of IowaGunnar GudmundssonRama Mallampalli - University of IowaLinda S. Powers - University of IowaGary W. Hunninghake - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.162(5), pp.3005-3012
- DOI
- 10.4049/jimmunol.162.5.3005
- PMID
- 10072552
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 03/01/1999
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984622754602771
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