Immune Netw.  2009 Apr;9(2):64-73. 10.4110/in.2009.9.2.64.

15-Deoxy-Delta(12,14)-Prostaglandin J2 Upregulates the Expression of LPS-Induced IL-8/CXCL8 mRNA in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats

Affiliations
  • 1Department of Microbiology, College of Medicine, and Aging-associated Vascular Disease Research Center, Yeungnam University, Daegu, Korea. heesun@med.yu.ac.kr

Abstract

BACKGROUND
15d-PGJ2 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-PGJ2 on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR. METHODS: Effect and action mechanism of 15d-PGJ2 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-PGJ2 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-PGJ2 in SHR VSMCs was mediated through PPAR gamma, and dependent on NF-kappaB activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-PGJ2 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-PGJ2/LPS. CONCLUSION: Our results indicate that the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPAR gamma and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-PGJ2/LPS-induced IL-8/CXCL8 expression in SHR VSMCs.

Keyword

15d-PGJ2; IL-8/CXCL8; vascular smooth muscle cells

MeSH Terms

Blotting, Western
Electrophoretic Mobility Shift Assay
Flow Cytometry
MAP Kinase Signaling System
Muscle, Smooth, Vascular
NADPH Oxidase
NF-kappa B
Phosphorylation
PPAR gamma
Prostaglandin D2
Rats, Inbred SHR
Real-Time Polymerase Chain Reaction
RNA, Messenger
NADPH Oxidase
NF-kappa B
PPAR gamma
Prostaglandin D2
RNA, Messenger
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