Lysophosphatidylcholine activates p38 and p42/44 mitogen- activated protein kinases in monocytic THP-1 cells, but only p38 activation is involved in its stimulated chemotaxis

Qing Jing, Sun Mei Xin, Wen Bo Zhang, Ping Wang, Yong Wen Qin, Gang Pei

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Oxidized LDLs (OxLDLs) have been shown to be involved in recruitment of blood monocytes into the arterial subendothelial space, which is the earliest step in atherogenesis, but the underlying molecular mechanisms are poorly understood. The present study demonstrated that lysophosphatidylcholine (LPC), a major phospholipid component of OxLDL, strongly evoked phosphorylation and activation of p38 and p42/44 mitogen- activated protein kinases in monocytic cells. The stimulation of p38 and p42/44 occurred in a dose- and time-dependent manner, reaching the maximal activation at 25 μg/mL LPC within 5 minutes. Interestingly, inhibition of p38 activation by OxLDL or LPC, using its selective inhibitors (SB203580 and SKF86002), completely blocked OxLDL- or LPC-stimulated chemotaxis of THP-1 cells, which was measured in a transwell chemotaxis assay. In contrast, inhibition of p42/44 activation by its potent inhibitor (PD98059) did not block OxLDL- or LPC-stimulated chemotaxis. Moreover, expression of a p38 dominant-negative mutant (p38AF) reduced cell chemotaxis significantly. In addition, activation of p38 by LPC was apparently mediated neither by scavenger receptors nor by tyrosine kinase receptors. It was, however, effectively blocked by pertussis toxin and substantially reduced by phospholipase C inhibitor (U73122) and phosphatidylinositol 3- kinase inhibitors (wortmannin and LY294002). LPC also inhibited forskolin-stimulated cAMP accumulation in a pertussis toxin- sensitive manner, indicating that Gi/Go proteins likely mediated the effects of LPC. Our results suggested that OxLDL/LPC efficiently activated both p38 and p42/44, but only the activation of p38 was functionally associated with OxLDL-/LPC- induced chemotaxis in THP-1 cells.

Original languageEnglish (US)
Pages (from-to)52-59
Number of pages8
JournalCirculation Research
Volume87
Issue number1
DOIs
StatePublished - Jul 7 2000
Externally publishedYes

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Keywords

  • Atherosclerosis
  • Chemotaxis
  • Lysophosphatidylcholine
  • Mitogen-activated protein kinase
  • Monocytes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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