15-Deoxy-Δ12,14-Prostaglandin J2 Upregulates the Expression of LPS-Induced IL-8/CXCL8 mRNA in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats
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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-κB 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 PPARγ, and dependent on NF-κB 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 LPSinduced 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 PPARγ 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.
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-κB 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 PPARγ, and dependent on NF-κB 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 LPSinduced 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 PPARγ 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.
참고문헌 (44)
- Alexander RW, "Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective", Hypertension, 25, pp.155~161 (1995)
- Capers Q 4th, "Monocyte chemoattractant protein-1 expression in aortic tissues of hypertensive rats", Hypertension, 30, pp.1397~1402 (1997)
- Rodríguez-Iturbe B, "Oxidative stress, renal infiltration of immune cells and salt-sensitive hypertension: all for one and one for all", Am J Physiol, 286, pp.F606~F616 (2004)
- Zhang Y, "Vascular hypertrophy in angiotensin II-induced hypertension is mediated by vascular smooth muscle cell-derived H2O2", Hypertension, 46, pp.732~737 (2005)
- Gerszten RE, "Pleiotropic effects of chemokines in vascular lesion development", Artherioscler Thromb Vasc Biol, 22, pp.528~529 (2002)
- Luster AD, "Chemokines - chemotactic cytokines that mediate inflammation", N Engl J Med, 338, pp.436~445 (1998)
- Gerszten RE, "MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions", Nature, 398, pp.718~723 (1999)
- Boekholdt S, "IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk prospective population study", Arterioscler Thromb Vasc Biol, 24, pp.1503~1508 (2004)
- Buemi M, "Effect of interleukin 8 and ICAM-1 on calcium-dependent outflow of K+ in erythrocytes from subjects with essential hypertension", Curr Med Res Opin, 20, pp.19~24 (2004)
- Kim HY, "Upregulation of Interleukin-8", CXCL8 in vascular smooth muscle cells from spontaneously hypertensive rats, 2008, pp.31, 515~523
- Dobrian AD, "Pioglitazone prevents hypertension and reduces oxidative stress in diet-induced obesity", Hypertension, 43, pp.48~56 (2004)
- Fukuda N, "Troglitazone inhibits growth and improves insulin signaling by suppression of angiotensin II action in vascular smooth muscle cells from spontaneously hypertensive rats", Atherosclerosis, 163, pp.229~239 (2002)
- Wakino S, "Pioglitazone lowers systemic asymmetric dimethylarginine by inducing dimethylarginine dimethylaminohydrolase in rats", Hypertens Res, 28, pp.255~262 (2005)
- Calnek DS, "Peroxisome proliferatorsactivated receptor gamma ligands increase release of nitric oxide from endothelial cells", Arterioscler Thromb Vasc Biol, 23, pp.52~57 (2003)
- Jiang C, "PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines", Nature, 391, pp.82~86 (1998)
- Chastine Bell-Parikh L, "Biosynthesis of 15-deoxy-delta 12,14- PGJ2 and the ligation of PPARgamma", J Clin Invest, 112, pp.945~955 (2003)
- Benkirane K, "PPAR-gamma inhibits ANG II-induced cell growth via SHIP2 and 4E-BP1", Am J Physiol Heart Circ Physiol, 290, pp.F390~F397 (2006)
- Law RE, "Expression and function of PPARgamma in rat and human vascular smooth muscle cells", Circulation, 101, pp.1311~1318 (2000)
- Lim HJ, "15d-PGJ2 stimulates HO-1 expression through p38 MAP kinase and Nrf-2 pathway in rat vascular smooth muscle cells", Toxicol and Appl Pharmacol, 223, pp.20~27 (2007)
- Cuzzocrea S, "The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) attenuates the development of acute and chronic inflammation", Mol Pharmacol, 61, pp.997~1007 (2002)
- Reilly CM, "Prostaglandin J2 inhibition of mesangial cell iNOS expression", Clin Immunol, 3, pp.337~345 (2001)
- Sawano H, "15-Deoxy-Delta12,14-prostaglandin J2 inhibits IL-1beta-induced cyclooxygenase-2 expression in mesangial cells", Kideny Int, 61, pp.1957~1967 (2002)
- Fu Y, "Upregulation of interleukin-8 expression by prostaglandin J2 (15d-PGJ2) in human THP-1 macrophages", Atherosclerosis, 160, pp.11~20 (2002)
- Harris SG, "15-deoxy-Delta 12,14-PGJ2 induces IL-8 production in human T cells by a mitogen-activated protein kinase pathway", J Immunol, 168, pp.1372~1379 (2002)
- Kim HY, "Upregulation of LPS-induced chemokine KC expression by 15-deoxy-delta12,14-prostaglandin J2 in mouse peritoneal macrophages", Immunol Cell Biol, 83, pp.286~293 (2005)
- Kim HY, "Upregulation of MIP-2 (CXCL2) expression by 15-deoxy-Delta(12,14)-prostaglandin J(2) in mouse peritoneal macrophages", Immunol Cell Biol, 85, pp.60~67 (2007)
- Kelly G, "Differential effects of 15-deoxy-Delta(12,14)-PGJ2 and a peroxisome proliferators-activated receptor gamma agonist on macrophage activation", J Leukoc Biol, 69, pp.631~638 (2001)
- Ricote M, "The peroxisome proliferator-activated receptor gamma (PPARgamma) as a regulator of monocyte", macrophage function, 1999, pp.66, 733~739
- Zhang X, "Differential regulation of chemokine gene expression by 15-deoxy-delta 12,14 prostaglandin J2", J Immunol, 166, pp.7104~7111 (2001)
- Wakino S, "Peroxisome proliferatior-activated receptor gamma ligands inhibit Rho", Rho kinase pathway by inducing protein tyrosine phosphatase SHP-2, 2004, pp.95, e45~e55
- Guyton K, "Differential effects of 15-deoxy-delta(12,14)-prostaglandin J2 and a peroxisome proliferator-activatedreceptor gamma agonist on macrophage activation", J Leukoc Biol, 69, pp.631~638 (2001)
- Kim, Hyo Young, "Upregulation of Lipopolysaccharide-Induced Interleukin-10 by ProstaglandinA1 in Mouse Peritoneal Macrophages", Journal of Microbiology and Biotechnology, 18(6), pp.1170~1178 (2008), 한국미생물·생명공학회
- Bureau F, "A proinflammatory role for the cyclopentenone prostaglandins at low micromolar concentrations: oxidative stress-induced extracellular signal-regulated kinase activation without NF-kappa B inhibition", J Immunol, 168, pp.5318~5325 (2002)
- Ricote M, "The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation", Nature, 391, pp.79~82 (1998)
- Straus DS, "15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signaling pathway", Proc Natl Acad Sci U S A, 97, pp.4844~4849 (2000)
- Wilmer WA, "A cyclopentenone prostaglandin activates mesangial MAP kinase independently of PPARgamma", Biochem Biophys Res Comm, 281, pp.57~62 (2001)
- Takeda K, "15-Deoxy-delta 12,14-prostaglandin J2 and thiazolidinediones activate the MEK", ERK pathway through phosphatidylinositol 3-kinase in vascular smooth muscle cells, 2001, pp.276, 48950~48955
- Jung YD, "Role of p38 MAPK, AP-1 and NF-kappaB in interleukin-1beta-induced IL-8 expression in human vascular smooth muscle cells", Cytokine, 18, pp.206~213 (2002)
- Zhao ML, "15-deoxy-delta (12,14)-PGJ2 inhibits astrocyte IL-1 signaling: inhibition of NF-kappaB and MAP kinase pathways and suppression of cytokine and chemokine expression", J Neuroimmunol, 153, pp.132~142 (2004)
- Thannickal VJ, "Reative oxygen species in cell signaling", Am J Physiol Lung Cell Mol Physiol, 279, pp.L1005~L1028 (2000)
- Cruzado MC, "Vascular smooth muscle cell NAD(P)H oxidase activity during the development of hypertension: effect of angiotensin II and role of insulinkike growth factor-1 receptor transactivation", Am J Hyertension, 18, pp.81~87 (2005)
- Kunsch C, "Oxidative stress as a regulator of gene expression in the vasculature", Circ Res, 85, pp.753~766 (1999)
- Seshiah PN, "Angiotensin II stimulation of NAD(P)H oxi dase activity upstream mediators", Circ Res, 91, pp.406~413 (2002)
- Touyz RM, "Ang II-stimulated generation of reactive oxygen species in Human vascular smooth muscle cells in mediated via PLD-dependent pathways", Hypertension, 34, pp.976~982 (1999)
