title: 3,4,5-Trihydroxycinnamic acid increases heme-oxygenase-1 (HO-1) and decreases macrophage infiltration in LPS-induced septic kidney.
abstract: We previously demonstrated that 3,4,5-trihydorxycinnamic acid (THC), a derivative of hydroxycinnamic acids, possesses protective effect in lipopolysaccharide (LPS)-induced endotoxemia models. However, the effects of THC in LPS-induced septic kidney are still unclear. Therefore, the present study was carried out to examine the effects of THC in LPS-challenged septic kidney using mesangial cell line and Balb/c mice. THC pretreatment effectively inhibited LPS-induced macrophage infiltration and the secretion of pro-inflammatory cytokines in the kidney of LPS-challenged animals. Pretreatment of rat mesangial cells with THC significantly attenuated LPS-induced PGE2 production and COX-2 expression. THC also significantly suppressed LPS-induced expression of MCP-1 in LPS-activated septic kidney and rat mesangial cells. In addition, THC significantly attenuated LPS-induced degradation of IκB-α in LPS-induced rat mesangial cells. THC also increased the expression of heme oxygenase-1 (HO-1) in LPS-challenged septic kidney and mesangial cells. Multiple signaling pathways including p38 and AKT have been observed to be involved in the THC-induced activation of HO-1 expression. The present data clearly demonstrate that THC protects LPS-challenged septic kidney by decreasing macrophage infiltration and increasing HO-1 expression, suggesting that THC might be a valuable therapeutic agent for compromised kidney in sepsis.
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Kangwon, 200-701, Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Kwon
authors.forename: Man Sup
authors.initials: MS
authors.lastname: Lim
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: So Young
authors.initials: SY
authors.lastname: Lim
authors.forename: Wanjoo
authors.initials: W
authors.lastname: Chun
mesh_terms: D000818:Animals; D002460:Cell Line; D002934:Cinnamates / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000201:enzymology* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis*; D050527:Mesangial Cells / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D012772:Shock, Septic / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002934:Cinnamates; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C029010:cinnamic acid; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone
references.citation: Biochem Biophys Res Commun. 2010 Jan 15;391(3):1400-4
references.pmid: 20026303
references.citation: Inflamm Res. 2012 Nov;61(11):1177-85
references.pmid: 22752115
references.citation: Mol Cell Biochem. 2014 May;390(1-2):143-53
references.pmid: 24474616
references.citation: Shock. 2002 May;17(5):433-8
references.pmid: 12022767
references.citation: Biol Pharm Bull. 2012;35(11):1941-6
references.pmid: 23123466
references.citation: J Immunol. 1995 Jul 1;155(1):316-24
references.pmid: 7541418
references.citation: Eur J Pharmacol. 2011 Jan 10;650(1):445-50
references.pmid: 20940016
references.citation: Sci Am. 1992 Aug;267(2):54-61
references.pmid: 1641625
references.citation: Biochem Pharmacol. 2004 Jan 1;67(1):175-81
references.pmid: 14667940
references.citation: Arch Pharm Res. 2010 Oct;33(10):1611-32
references.pmid: 21052937
references.citation: Int Immunopharmacol. 2008 Mar;8(3):484-94
references.pmid: 18279803
references.citation: Eur J Pharmacol. 2010 Sep 15;643(1):21-8
references.pmid: 20599928
references.citation: Toxicol Appl Pharmacol. 2014 May 15;277(1):95-107
references.pmid: 24675710
references.citation: Annu Rev Cell Biol. 1994;10:405-55
references.pmid: 7888182
references.citation: Kidney Int. 2006 Mar;69(6):974-80
references.pmid: 16528246
references.citation: Nephrol Dial Transplant. 2011 Apr;26(4):1162-72
references.pmid: 20864551
references.citation: Int Immunopharmacol. 2014 Apr;19(2):253-61
references.pmid: 24508058
references.citation: Cell Prolif. 2013 Oct;46(5):595-605
references.pmid: 24033467
references.citation: Neurochem Int. 2011 Feb;58(2):153-60
references.pmid: 21093515
references.citation: Mol Med Rep. 2013 Jan;7(1):242-6
references.pmid: 23124098
references.citation: Biochem Biophys Res Commun. 2007 Jun 29;358(2):615-9
references.pmid: 17499610
references.citation: Oncogene. 1995 Jul 6;11(1):97-106
references.pmid: 7624137
references.citation: Int Immunopharmacol. 2007 Aug;7(8):1092-101
references.pmid: 17570326
references.citation: Kidney Int Suppl. 1998 May;66:S38-42
references.pmid: 9573571
references.citation: Acta Pharmacol Sin. 2009 Feb;30(2):228-34
references.pmid: 19122672
references.citation: Biochem Pharmacol. 2011 Oct 1;82(7):769-77
references.pmid: 21763292
references.citation: Am J Physiol Renal Physiol. 2006 Jun;290(6):F1453-62
references.pmid: 16418300
references.citation: Peptides. 2010 Nov;31(11):2094-9
references.pmid: 20713105
references.citation: Mol Pharmacol. 2009 Jul;76(1):173-82
references.pmid: 19366789
references.citation: Korean J Physiol Pharmacol. 2011 Feb;15(1):9-15
references.pmid: 21461235
references.citation: Biochem Pharmacol. 2008 Oct 15;76(8):967-73
references.pmid: 18755157
references.citation: N Engl J Med. 2004 Jul 8;351(2):159-69
references.pmid: 15247356