본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

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  );
  • 초록

    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.


  • 주제어

    15d- $PGJ_2$ .   IL-8/CXCL8 .   vascular smooth muscle cells.  

  • 참고문헌 (44)

    1. Alexander RW: Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension 25;155-161, 1995 
    2. Rodr$\acute{i}$guez-Iturbe B, Vaziri ND, Herrera-Acosta J, Johnson RJ: Oxidative stress, renal infiltration of immune cells and salt-sensitive hypertension: all for one and one for all. Am J Physiol 286;F606-F616, 2004 
    3. Gerszten RE, Garcia-Zepeda EA, Lim YC, Yoshida M, Ding HA, Gimbrone MA, Luster AD, Luscinskas FW, Rosenzweig A: MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 398; 718-723, 1999 
    4. Dobrian AD, Schriver SD, Khraibi AA, Prewitt RL: Pioglitazone prevents hypertension and reduces oxidative stress in diet-induced obesity. Hypertension 43;48-56, 2004 
    5. Fukuda N, Hu WY, Teng J, Chikara S, Nakayama K, Kanmatsuse K: Troglitazone inhibits growth and improves insulin signaling by suppression of angiotensin II action in vascular smooth muscle cells from spontaneously hypertensive rats. Atherosclerosis 163;229-239, 2002 
    6. Cuzzocrea S, Wayman NS, Mazzon E, Dugo L, Paola R, Serraino I, Britti D, Chatterjee PK, Caputi AP, Thiemermann C: The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) attenuates the development of acute and chronic inflammation. Mol Pharmacol 61;997-1007, 2002 
    7. Harris SG, Smith RS, Phipps RP: 15-deoxy-Delta 12,14-PGJ2 induces IL-8 production in human T cells by a mitogen-activated protein kinase pathway. J Immunol 168; 1372-1379, 2002 
    8. Ricote M, Huang JT, Welch JS, Glass CK: The peroxisome proliferator-activated receptor gamma (PPARgamma) as a regulator of monocyte/macrophage function. J Leukoc Biol 66;733-739, 1999 
    9. Straus DS, Pascual G, Li M, Welch JS, Ricote M, Hsiang CH, Sengchanthalangsy LL, Ghosh G, Galss CK: 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;4844-4849, 2000 
    10. Takeda K, Ichiki T, Tokunou T, Iino N, Takeshita A: 15-Deoxy-delta 12,14-prostaglandin J2 and thiazolidinediones activate the MEK/ERK pathway through phosphatidylinositol 3-kinase in vascular smooth muscle cells. J Biol Chem 276;48950-48955, 2001 
    11. Jung YD, Fan F, McConkey DJ, Jean ME, Liu W, Reinmuth N, Stoeltzing O, Ahmad SA, Parikh AA, Mukaida N, Ellis LM: Role of p38 MAPK, AP-1 and NF-kappaB in interleukin-1beta-induced IL-8 expression in human vascular smooth muscle cells. Cytokine 18;206-213, 2002 
    12. Kunsch C, Medford RM: Oxidative stress as a regulator of gene expression in the vasculature. Circ Res 85;753-766, 1999 
    13. Seshiah PN, Weber DS, Rocic P, Valppu L, Taniyama Y, Griendling KK: Angiotensin II stimulation of NAD(P)H oxi dase activity upstream mediators. Circ Res 91;406-413, 2002 
    14. Benkirane K, Amiri F, Diep QN, Mabrouk ME, Schiffrin EL:PPAR-gamma inhibits ANG II-induced cell growth via SHIP2 and 4E-BP1. Am J Physiol Heart Circ Physiol 290;H390-H397, 2006 
    15. Lim HJ, Lee KS, Lee S, Park JH, Choi HE, Go SH, Kwak HJ, Park HY: 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;20-27, 2007 
    16. Wilmer WA, Dixon C, Lu L, Hilbelink T, Rovin BH: A cyclopentenone prostaglandin activates mesangial MAP kinase independently of PPARgamma. Biochem Biophys Res Comm 281;57-62, 2001 
    17. Capers Q 4th, Alexander RW, Lou P, De Leon H, Wilcox JN, Ishizaka N, Howard AB, Taylor WR: Monocyte chemoattractant protein-1 expression in aortic tissues of hypertensive rats. Hypertension 30;1397-1402, 1997 
    18. Zhang Y, Griendling KK, Dikalova A, Owens GK, Talyor WR: Vascular hypertrophy in angiotensin II-induced hypertension is mediated by vascular smooth muscle cell-derived H2O2. Hypertension 46;732-737, 2005 
    19. Law RE, Goetze S, Xi, XP, Jackson S, Kawano Y, Demer L, Fishbein MC, Meehan WP, Hsueh WA: Expression and function of PPARgamma in rat and human vascular smooth muscle cells. Circulation 101;1311-1318, 2000 
    20. Kim HY, Kim HS: Upregulation of MIP-2 (CXCL2) expression by 15-deoxy-Delta(12,14)-prostaglandin J(2) in mouse peritoneal macrophages. Immunol Cell Biol 85;60-67, 2007 
    21. Boekholdt S, Peters R, Hack CE, Day NE, Luben R, Bingham SA, Wareham NJ, Reitsma PH, Khaw K: 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;1503-1508, 2004 
    22. Calnek DS, Mazzella L, Roser S, Roman J, Hart CM: Peroxisome proliferatorsactivated receptor gamma ligands increase release of nitric oxide from endothelial cells. Arterioscler Thromb Vasc Biol 23;52-57, 2003 
    23. Gerszten RE: Pleiotropic effects of chemokines in vascular lesion development. Artherioscler Thromb Vasc Biol 22; 528-529, 2002 
    24. Kim HY, Kang YJ, Song IH, Choi HC, Kim HS: Upregulation of Interleukin-8/CXCL8 in vascular smooth muscle cells from spontaneously hypertensive rats. Hypertens Res 31;515-523, 2008 
    25. Sawano H, Haneda M, Sugimoto T, Inoki K, Koya D, Kikkawa R: 15-Deoxy-Delta12,14-prostaglandin J2 inhibits IL-1beta-induced cyclooxygenase-2 expression in mesangial cells. Kideny Int 61;1957-1967, 2002 
    26. Zhang X, Wang JM, Gong WH, Mukaida N, Young HA:Differential regulation of chemokine gene expression by 15-deoxy-delta 12,14 prostaglandin J2. J Immunol 166;7104-7111, 2001 
    27. Guyton K, Bond R, Reilly C, Gileson G, Halushka P, Cook J: Differential effects of 15-deoxy-delta(12,14)-prostaglandin J2 and a peroxisome proliferator-activatedreceptor gamma agonist on macrophage activation. J Leukoc Biol 69;631-638, 2001 
    28. Wakino S, Hayashi K, Tatematsu S, Hasegawa K, Takamatsu I, Kanda T, Homma K, Yoshioka K, Sugano N, Saruta T: Pioglitazone lowers systemic asymmetric dimethylarginine by inducing dimethylarginine dimethylaminohydrolase in rats. Hypertens Res 28;255-262, 2005 
    29. Fu Y, Luo N, Lopes-Virella MF: Upregulation of interleukin-8 expression by prostaglandin J2 (15d-PGJ2) in human THP-1 macrophages. Atherosclerosis 160;11-20, 2002 
    30. Chastine Bell-Parikh L, Ide T, Lawson JA, Mcncmara P, Reilly M, Fitzgerald GA: Biosynthesis of 15-deoxy-delta 12,14- PGJ2 and the ligation of PPARgamma. J Clin Invest 112;945-955, 2003 
    31. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK: The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391;79-82, 1998 
    32. Kelly G, Robert B, Chris R, Gary G, Perry H, James C:Differential effects of 15-deoxy-Delta(12,14)-PGJ2 and a peroxisome proliferators-activated receptor gamma agonist on macrophage activation. J Leukoc Biol 69;631-638, 2001 
    33. Touyz RM, Schiffrin EL: Ang II-stimulated generation of reactive oxygen species in Human vascular smooth muscle cells in mediated via PLD-dependent pathways. Hypertension 34;976-982, 1999 
    34. Luster AD: Chemokines - chemotactic cytokines that mediate inflammation. N Engl J Med 338;436-445, 1998 
    35. Kim HY, Kim JR, Kim HS: Upregulation of lipopolysaccharide-induced interleukin-10 by prostaglandin A1 in mouse peritoneal macrophages. J Microbiol Biotech 18;1170-1178, 2008 
    36. Zhao ML, Brosnan CF, Lee SC: 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;132-142, 2004 
    37. Bureau F, Desmet C, Melotte D, Jaspar F, Volanti C, Vanderplasschen A, Pastoret PP, Piette J, Lekeux P: 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;5318-5325, 2002 
    38. Jiang C, Ting AT, Seed B: PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391; 82-86, 1998 
    39. Reilly CM, Oates JC, Suidan J, Crosby MB, Halushka PV, Gilkeson GS: Prostaglandin J2 inhibition of mesangial cell iNOS expression. Clin Immunol 3;337-345, 2001 
    40. Buemi M, Marino D, Floccari F, Ruello A, Nosto L, Aloisi C, Marino MT, Di Pasquale G, Corica F, Frisina 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;19-24, 2004 
    41. Thannickal VJ, Fanburg BL: Reative oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 279;L1005-L1028, 2000 
    42. Cruzado MC, Risler NR, Miatello RM, Yao G, Schiffrin EL, Touyz RM: 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;81-87, 2005 
    43. Kim HY, Kim HK, Kim JR, Kim HS: Upregulation of LPS-induced chemokine KC expression by 15-deoxy-delta12,14-prostaglandin J2 in mouse peritoneal macrophages. Immunol Cell Biol 83;286-293, 2005 
    44. Wakino S, Hayashi H, Kanda T, Tatematsu S, Homma K, Yoshioka K, Taksmatsu I, Saruta T: Peroxisome proliferatior-activated receptor gamma ligands inhibit Rho/Rho kinase pathway by inducing protein tyrosine phosphatase SHP-2. Circulation 95;e45-e55, 2004 

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기