title: Cyclopentenone prostaglandins PGA2 and 15-deoxy-delta12,14 PGJ2 suppress activation of murine microglia and astrocytes: implications for multiple sclerosis.
abstract: The cyclopentenone prostaglandin (cPG) 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) has been identified as a potent antiinflammatory agent that is able to inhibit the activation of macrophages and microglia. Additionally, 15d-PGJ(2) is able to ameliorate the clinical manifestations of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Many biological effects of 15d-PGJ(2) have been attributed to the peroxisome proliferator activated receptor-gamma (PPAR-gamma). PGA(2), like 15d-PGJ(2), is a cPG. The aim of this study is to compare the relative effectiveness of these two cPGs in inhibiting the inflammatory response of mouse microglia and astrocytes, two cell types that upon activation may contribute to the pathology of EAE and MS. Purified primary mouse microglia and astrocytes were treated with either 15d-PGJ(2) or PGA(2) and then stimulated with either lipopolysaccharide (LPS) or a combination of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. The results show that 15d-PGJ(2) and PGA(2) both potently inhibited the production of nitrite, as well as proinflammatory cytokines and chemokines, from microglia and astrocytes. Generally, regulation of NO production was more sensitive to 15d-PGJ(2), however, cytokine and chemokine production was more sensitive to PGA(2) treatment. These results demonstrate for the first time that PGA(2) is a potent antiinflammatory mediator.
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205-7101, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Storer
authors.forename: Jihong
authors.initials: J
authors.lastname: Xu
authors.forename: Janet A
authors.initials: JA
authors.lastname: Chavis
authors.forename: Paul D
authors.initials: PD
authors.lastname: Drew
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011454:Prostaglandins A / Q000494:pharmacology*
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D018925:Chemokines; D011454:Prostaglandins A; D009569:Nitric Oxide; C100008:prostaglandin A2; D015230:Prostaglandin D2
references.citation: J Neuroimmunol. 1998 Jun 1;86(1):20-9
references.pmid: 9655469
references.citation: Biochem Biophys Res Commun. 1998 Aug 28;249(3):817-21
references.pmid: 9731219
references.citation: Mult Scler. 1998 Jun;4(3):203-11
references.pmid: 9762675
references.citation: J Immunol. 1998 Dec 15;161(12):6480-6
references.pmid: 9862671
references.citation: J Neuroimmunol. 1998 Dec 1;92(1-2):98-108
references.pmid: 9916884
references.citation: Am J Pathol. 1999 Jan;154(1):45-51
references.pmid: 9916917
references.citation: J Clin Invest. 1999 Mar;103(6):807-15
references.pmid: 10079101
references.citation: Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4668-73
references.pmid: 10200320
references.citation: Nat Med. 1999 Jun;5(6):698-701
references.pmid: 10371510
references.citation: J Clin Invest. 1999 Aug;104(4):383-9
references.pmid: 10449430
references.citation: J Clin Immunol. 1999 Sep;19(5):273-9
references.pmid: 10535603
references.citation: J Immunol. 2000 Jan 15;164(2):1046-54
references.pmid: 10623855
references.citation: Glia. 2000 Feb 15;29(4):293-304
references.pmid: 10652440
references.citation: Neuroreport. 2000 Jan 17;11(1):89-91
references.pmid: 10683836
references.citation: J Neuroimmunol. 1999 Dec;100(1-2):21-35
references.pmid: 10695712
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4844-9
references.pmid: 10781090
references.citation: Brain Res. 2000 Jun 9;867(1-2):115-21
references.pmid: 10837804
references.citation: J Neurosci Res. 2000 Jul 1;61(1):67-74
references.pmid: 10861801
references.citation: J Clin Invest. 2000 Jul;106(2):189-97
references.pmid: 10903334
references.citation: Eur J Neurosci. 2000 Jul;12(7):2215-23
references.pmid: 10947800
references.citation: Cell Mol Life Sci. 1999 Oct 1;56(1-2):5-21
references.pmid: 11213261
references.citation: J Neuroimmunol. 2001 Apr 2;115(1-2):28-35
references.pmid: 11282151
references.citation: J Neuroimmunol. 2001 Apr 2;115(1-2):192-8
references.pmid: 11282170
references.citation: Med Res Rev. 2001 May;21(3):185-210
references.pmid: 11301410
references.citation: J Leukoc Biol. 2001 Apr;69(4):631-8
references.pmid: 11310850
references.citation: J Immunol. 2001 Jun 15;166(12):7104-11
references.pmid: 11390455
references.citation: J Exp Med. 2001 Sep 3;194(5):F27-30
references.pmid: 11535639
references.citation: Glia. 2001 Nov;36(2):180-90
references.pmid: 11596126
references.citation: J Immunol. 2002 Mar 1;168(5):2508-15
references.pmid: 11859145
references.citation: J Leukoc Biol. 2002 Apr;71(4):677-85
references.pmid: 11927655
references.citation: Genes Immun. 2002 Apr;3(2):59-70
references.pmid: 11960303
references.citation: Curr Top Microbiol Immunol. 2002;265:23-48
references.pmid: 12014193
references.citation: Ann Neurol. 2002 Jun;51(6):694-702
references.pmid: 12112074
references.citation: J Neurocytol. 2001 Aug;30(8):671-83
references.pmid: 12118155
references.citation: Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:611-7
references.pmid: 12432947
references.citation: Semin Immunol. 2003 Feb;15(1):23-32
references.pmid: 12495638
references.citation: J Neurosci Res. 2003 Feb 1;71(3):315-25
references.pmid: 12526021
references.citation: Arch Neurol. 2003 Jan;60(1):132-6
references.pmid: 12533101
references.citation: J Neuroimmunol. 2003 Feb;135(1-2):166-71
references.pmid: 12576238
references.citation: Biochem Biophys Res Commun. 2003 Mar 7;302(2):415-20
references.pmid: 12604364
references.citation: Nat Med. 2003 Mar;9(3):287-93
references.pmid: 12598893
references.citation: J Biol Chem. 2003 Apr 25;278(17):14747-52
references.pmid: 12584205
references.citation: J Immunol. 2003 Jul 15;171(2):979-88
references.pmid: 12847270
references.citation: J Neurochem. 2003 Aug;86(4):907-16
references.pmid: 12887689
references.citation: Mult Scler. 2003 Aug;9(4):332-41
references.pmid: 12926837
references.citation: Neuropathol Appl Neurobiol. 2003 Oct;29(5):434-44
references.pmid: 14507335
references.citation: J Neurochem. 2003 Nov;87(3):742-51
references.pmid: 14535956
references.citation: J Neuroimmunol. 2003 Dec;145(1-2):86-90
references.pmid: 14644034
references.citation: Exp Biol Med (Maywood). 2004 Jan;229(1):12-20
references.pmid: 14709772
references.citation: J Neuroimmunol. 2004 Mar;148(1-2):116-26
references.pmid: 14975592
references.citation: Neurosci Lett. 2004 Mar 18;358(1):58-62
references.pmid: 15016434
references.citation: FEBS Lett. 2004 Mar 26;562(1-3):211-5
references.pmid: 15044028
references.citation: J Cell Biol. 1980 Jun;85(3):890-902
references.pmid: 6248568
references.citation: Annu Rev Immunol. 1992;10:153-87
references.pmid: 1375472
references.citation: J Immunol. 1993 Mar 15;150(6):2525-33
references.pmid: 8450228
references.citation: Ann Neurol. 1995 Apr;37(4):424-35
references.pmid: 7536402
references.citation: Neurology. 1995 Jun;45(6 Suppl 6):S16-21
references.pmid: 7540265
references.citation: J Immunol. 1995 Dec 15;155(12):5769-76
references.pmid: 7499865
references.citation: Cell. 1995 Dec 1;83(5):803-12
references.pmid: 8521497
references.citation: Cell. 1995 Dec 1;83(5):813-9
references.pmid: 8521498
references.citation: Trends Neurosci. 1996 Aug;19(8):331-8
references.pmid: 8843602
references.citation: Brain Behav Immun. 1995 Dec;9(4):315-30
references.pmid: 8903849
references.citation: J Mol Med (Berl). 1997 Mar;75(3):165-73
references.pmid: 9106073
references.citation: J Exp Med. 1997 Nov 3;186(9):1585-90
references.pmid: 9348316
references.citation: Nature. 1998 Jan 1;391(6662):79-82
references.pmid: 9422508
references.citation: Nature. 1998 Jan 1;391(6662):82-6
references.pmid: 9422509
references.citation: J Neurosci Res. 1998 Jan 15;51(2):147-53
references.pmid: 9469568
references.citation: J Immunol. 1998 Mar 15;160(6):2940-6
references.pmid: 9510198
references.citation: Biochim Biophys Acta. 1998 Apr 1;1397(1):31-42
references.pmid: 9545524
references.citation: Eur J Immunol. 1998 Apr;28(4):1332-8
references.pmid: 9565373
references.citation: J Neuroimmunol. 1998 Apr 15;84(2):238-49
references.pmid: 9628469