title: 15-Deoxy-Delta-Prostaglandin J(2) Upregulates the Expression of LPS-Induced IL-8/CXCL8 mRNA in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats.
abstract: BACKGROUND
  15d-PGJ(2) has been known to act as an anti-inflammatory agent and has anti-hypertensive effects. As a result of these properties, we examined the effect of 15d-PGJ(2) on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR.
  
  
  METHODS
  Effect and action mechanism of 15d-PGJ(2) on the expression of LPS-induced IL-8/CXCL8 mRNA in VSMCs from SHR and WKY were examined by using real-time polymerase chain reaction, electrophoretic mobility shift assay for NF-kappaB avtivity, Western blotting analysis for ERK and p38 phosphorylation and flow cytometry for NAD(P)H oxidase activity.
  
  
  RESULTS
  15d-PGJ(2) decreased the expression of LPS-induced IL-8/CXCL8 mRNA in WKY VSMCs, but increased the expression of LPS-induced IL-8/CXCL8 mRNA in SHR VSMCs. The upregulatory effect of 15d-PGJ(2) in SHR VSMCs was mediated through PPARgamma, and dependent on NF-kappaB activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-PGJ(2) on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-PGJ(2) on LPS-induced IL-8/CXCL8 mRNA expression in SHR VSMCs, and an increase in NAD(P)H oxidase activity was detected in SHR VSMCs treated with 15d-PGJ(2)/LPS.
  
  
  CONCLUSIONS
  Our results indicate that the upregulatory effect of 15d-PGJ(2) on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPARgamma and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-PGJ(2)/LPS-induced IL-8/CXCL8 expression in SHR VSMCs.
authors.affiliation: Department of Microbiology, College of Medicine, and Aging-associated Vascular Disease Research Center, Yeungnam University, Daegu, Korea.
authors.forename: Jung Hae
authors.initials: JH
authors.lastname: Kim
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim