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http://dx.doi.org/10.4110/in.2009.9.2.64

15-Deoxy-${\Delta}^{12,14}$-Prostaglandin $J_2$ Upregulates the Expression of LPS-Induced IL-8/CXCL8 mRNA in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats  

Kim, Jung-Hae (Department of Microbiology, College of Medicine, and Aging-associated Vascular Disease Research Center, Yeungnam University)
Kim, Hee-Sun (Department of Microbiology, College of Medicine, and Aging-associated Vascular Disease Research Center, Yeungnam University)
Publication Information
IMMUNE NETWORK / v.9, no.2, 2009 , pp. 64-73 More about this Journal
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-${\kappa}B$ 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 PPAR${\gamma}$, and dependent on NF-${\kappa}B$ 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. Conclusion: 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 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-$PGJ_2$/LPS-induced IL-8/CXCL8 expression in SHR VSMCs.
Keywords
15d-$PGJ_2$; IL-8/CXCL8; vascular smooth muscle cells;
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