title: Annexin A1: potential for glucocorticoid sparing in RA.
abstract: Glucocorticoids have broad-ranging and powerful anti-inflammatory and immunomodulatory effects. Unsurprisingly, therefore, glucocorticoids are widely and persistently used to treat a large number of inflammatory diseases, including rheumatoid arthritis (RA), despite the well-described adverse effects of these drugs. Annexin A1 is a glucocorticoid-induced molecule that is known to replicate many of the described anti-inflammatory effects of glucocorticoids. In addition to the well-documented roles of this protein in neutrophil function, emerging evidence suggests that annexin A1 is involved in the modulation of T-cell function and the adaptive immune responses relevant to RA. Interest in annexin A1 was renewed after the delineation of the receptors for this protein. This breakthrough also led to advances in our understanding of anti-inflammatory annexin A1 mimetic peptides and agonistic compounds targeting these receptors, particularly those specific for the receptor N-formyl peptide receptor 2 (FPR2). Herein, we review the current knowledge of the biological activities of annexin A1 and their relevance to RA pathogenesis. We also discuss the potential of annexin A1 mimics and strategies aimed at potentiating annexin A1 signalling to become viable approaches to minimizing glucocorticoid use in RA and other inflammatory disorders.
authors: Centre for Inflammatory Diseases, Department of Medicine, Southern Clinical School, Monash University Faculty of Medicine, Nursing and Health Sciences, Monash Medical Centre, Clayton, VIC 3168, Australia.
authors: Yuan H
authors: YH
authors: Yang
authors: Eric
authors: E
authors: Morand
authors: Michelle
authors: M
authors: Leech
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D017305:Annexin A1 / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology*; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D044042:Receptors, Formyl Peptide / Q000502:physiology; D044067:Receptors, Lipoxin / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D017305:Annexin A1; C105101:FPR2 protein, human; D005938:Glucocorticoids; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin
references: Nature. 1986 Mar 6-12;320(6057):77-81
references: 2936963
references: Br J Pharmacol. 2013 Jan;168(1):238-52
references: 22924634
references: J Exp Med. 1994 Jul 1;180(1):253-60
references: 8006586
references: J Clin Invest. 2013 Jan;123(1):443-54
references: 23241962
references: J Immunol. 2013 Feb 1;190(3):997-1007
references: 23267026
references: Lancet. 1990 Jun 16;335(8703):1416-8
references: 1972208
references: Eur J Immunol. 2007 Nov;37(11):3131-42
references: 17948261
references: Mol Pharmacol. 2010 Feb;77(2):159-70
references: 19903830
references: Inflammation. 1997 Dec;21(6):583-96
references: 9429906
references: J Pharmacol Sci. 2009 Nov;111(3):317-21
references: 19926937
references: J Immunol. 2008 Oct 1;181(7):5035-44
references: 18802107
references: Mol Cell. 2000 May;5(5):831-40
references: 10882119
references: Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19317-22
references: 22084093
references: Int Immunopharmacol. 2011 Jan;11(1):55-66
references: 20974309
references: Nature. 1980 Sep 11;287(5778):147-9
references: 6893620
references: Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6506-11
references: 23533277
references: J Neuroimmunol. 1996 Sep;69(1-2):157-64
references: 8823388
references: Blood. 2006 Mar 1;107(5):2123-30
references: 16278303
references: Ann Rheum Dis. 2012 Nov;71(11):1872-80
references: 22562975
references: Immunity. 1999 Apr;10(4):451-61
references: 10229188
references: FASEB J. 2007 Apr;21(4):968-75
references: 17215481
references: Blood. 2008 Sep 15;112(6):2512-9
references: 18594025
references: FASEB J. 2010 Nov;24(11):4240-9
references: 20570963
references: J Immunol. 1983 Apr;130(4):1930-6
references: 6220071
references: J Cell Physiol. 1990 Jan;142(1):70-7
references: 2137129
references: Nat Rev Immunol. 2009 Jan;9(1):62-70
references: 19104500
references: FASEB J. 2003 Aug;17(11):1544-6
references: 12824302
references: Clin Exp Allergy. 2001 Jul;31(7):1116-25
references: 11468004
references: Ann Rheum Dis. 2008 Nov;67(11):1516-23
references: 18625622
references: Cell. 2011 Apr 15;145(2):224-41
references: 21496643
references: J Immunol. 2011 Apr 15;186(8):4905-14
references: 21398608
references: Cancer Res. 2010 Mar 15;70(6):2379-88
references: 20215502
references: FASEB J. 2007 Jun;21(8):1751-8
references: 17317721
references: Biochim Biophys Acta. 1997 Jun 27;1357(2):129-54
references: 9223619
references: Ann Rheum Dis. 2009 Jul;68(7):1119-24
references: 18684744
references: Bioorg Med Chem Lett. 2006 Jul 15;16(14):3713-8
references: 16697190
references: J Immunol. 1993 Feb 1;150(3):992-9
references: 8423349
references: J Leukoc Biol. 2012 Aug;92(2):249-58
references: 22493082
references: Pulm Pharmacol Ther. 2012 Aug;25(4):303-11
references: 22546484
references: Arthritis Rheum. 2000 Nov;43(11):2537-42
references: 11083278
references: Am J Pathol. 2005 Jun;166(6):1607-17
references: 15920146
references: Nat Rev Rheumatol. 2012 Nov;8(11):645-55
references: 23045254
references: J Immunol. 2007 Apr 1;178(7):4595-605
references: 17372018
references: J Immunol. 2006 Apr 1;176(7):4410-8
references: 16547279
references: Arthritis Rheum. 2004 Nov;50(11):3408-17
references: 15529366
references: Mediators Inflamm. 2006;2006(2):73835
references: 16883066
references: J Exp Med. 1999 Jan 18;189(2):395-402
references: 9892621
references: Pharmacol Rev. 2009 Jun;61(2):119-61
references: 19498085
references: BMC Immunol. 2011 Oct 19;12:59
references: 22011168
references: Ann Rheum Dis. 2009 Dec;68(12):1833-8
references: 19066177
references: Discov Med. 2012 Feb;13(69):123-33
references: 22369971
references: Arthritis Rheum. 1999 Jul;42(7):1538-44
references: 10403283
references: Clin Immunol Immunopathol. 1995 Aug;76(2):195-202
references: 7614738
references: Arthritis Res Ther. 2009;11(5):250
references: 19849822
references: Front Immunol. 2012 Nov 27;3:354
references: 23230437
references: J Biol Chem. 2012 Jul 13;287(29):24690-7
references: 22610094
references: J Neuroinflammation. 2009 Nov 13;6:33
references: 19912648
references: J Immunol. 1993 Oct 15;151(8):4306-14
references: 8409403
references: J Immunol. 2008 Aug 15;181(4):2813-20
references: 18684973
references: J Immunol. 2012 Feb 15;188(4):1799-808
references: 22262660
references: J Exp Med. 1999 Sep 6;190(5):741-7
references: 10477558
references: Rheumatology (Oxford). 2008 May;47(5):636-9
references: 18390587
references: Nature. 1979 Mar 29;278(5703):456-9
references: 450050
references: Blood. 2007 Feb 1;109(3):1095-102
references: 17008549
references: Arthritis Rheum. 2004 Mar;50(3):976-84
references: 15022342
references: Endocrine. 2012 Apr;41(2):183-90
references: 22169965
references: Br J Pharmacol. 1996 Jun;118(3):605-10
references: 8762084
references: J Immunol. 2009 Jul 15;183(2):1435-45
references: 19553536
references: Nat Med. 2002 Nov;8(11):1296-302
references: 12368905
references: Biochem Biophys Res Commun. 2012 Jan 20;417(3):1024-9
references: 22222376
references: Ann Rheum Dis. 1995 Oct;54(10):841-5
references: 7492225
references: Nat Med. 1996 Nov;2(11):1259-62
references: 8898757
references: J Cell Physiol. 2013 Feb;228(2):476-84
references: 22777765
references: Arthritis Rheum. 1992 Nov;35(11):1395-7
references: 1445462
references: J Immunol. 2012 Jan 1;188(1):135-45
references: 22116825
references: J Immunol. 2010 Mar 1;184(5):2611-2619
references: 20107188
references: Br J Pharmacol. 2009 Oct;158(4):936-46
references: 19845684
references: Pharmacol Rev. 2006 Sep;58(3):463-87
references: 16968948
references: Arthritis Rheum. 2010 Aug;62(8):2192-205
references: 20506322
references: FASEB J. 2003 Feb;17(2):253-5
references: 12475898
references: Mol Pharmacol. 2011 Jan;79(1):77-90
references: 20943772
references: Arthritis Rheum. 1999 Jun;42(6):1071-9
references: 10366098
references: Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):832-41
references: 23277546
references: Clin Exp Allergy. 2011 Dec;41(12):1793-803
references: 22092555
references: Arthritis Rheum. 2008 Apr;58(4):953-63
references: 18383390
references: Arthritis Rheum. 1994 Feb;37(2):207-11
references: 8129776
references: Biochem J. 2003 May 1;371(Pt 3):927-35
references: 12553880
references: Physiol Rev. 2002 Apr;82(2):331-71
references: 11917092