title: Proline-Glycine-Proline (PGP) and High Mobility Group Box Protein-1 (HMGB1): Potential Mediators of Cystic Fibrosis Airway Inflammation.
abstract: Cystic fibrosis (CF) is chronic lung disease characterized by an unrelenting neutrophil-predominant airway inflammatory response. This inflammation leads to extracellular matrix (ECM) remodeling and eventually to the development of bronchiectasis. While many components of the immune response in CF have been well-characterized, recent data suggests that small molecules may play an important and underappreciated role in this inflammation. This review will examine two novel molecules: proline-glycine-proline (PGP) and high mobility group box protein-1 (HMGB1), and their potential impact in CF lung disease. This review will provide a brief overview of CF lung disease and background on both HMGB1 and PGP. It will then focus on these molecules in a murine model of CF-like airway disease and in human biological specimens from CF individuals. Finally, this manuscript will address possible mechanisms for therapeutic targeting of these bioactive mediators.
authors.affiliation: Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Amit
authors.initials: A
authors.lastname: Gaggar
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rowe
authors.forename: Hardision
authors.initials: H
authors.lastname: Matthew
authors.forename: J Edwin
authors.initials: JE
authors.lastname: Blalock
references.citation: Mol Med. 2003 Jan-Feb;9(1-2):37-45
references.pmid: 12765338
references.citation: Eur Respir J. 2008 Sep;32(3):783-95
references.pmid: 18757703
references.citation: Science. 1999 Jul 9;285(5425):248-51
references.pmid: 10398600
references.citation: J Cancer Res Clin Oncol. 1991;117(3):249-53
references.pmid: 1674512
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):296-301
references.pmid: 14695889
references.citation: Nat Med. 2004 Nov;10(11):1216-21
references.pmid: 15502843
references.citation: Curr Drug Targets. 2004 Aug;5(6):581-8
references.pmid: 15270205
references.citation: Am J Respir Cell Mol Biol. 1993 Nov;9(5):511-9
references.pmid: 8217192
references.citation: Proc Natl Acad Sci U S A. 1978 Feb;75(2):871-5
references.pmid: 204938
references.citation: Respir Res. 2009 May 18;10:38
references.pmid: 19450278
references.citation: Lancet. 1985 Sep 28;2(8457):686-8
references.pmid: 2863676
references.citation: Pharmacol Ther. 2009 Feb;121(2):132-46
references.pmid: 19026684
references.citation: Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):2111-8
references.pmid: 8520783
references.citation: J Clin Invest. 2002 Mar;109(5):661-70
references.pmid: 11877474
references.citation: J Immunol. 2009 Apr 1;182(7):4423-31
references.pmid: 19299743
references.citation: Arthritis Rheum. 2002 Oct;46(10):2598-603
references.pmid: 12384917
references.citation: Novartis Found Symp. 2007;280:73-85; discussion 85-91, 160-4
references.pmid: 17380789
references.citation: Am J Physiol Cell Physiol. 2003 Apr;284(4):C870-9
references.pmid: 12620891
references.citation: Stroke. 2008 Mar;39(3):951-8
references.pmid: 18258837
references.citation: J Lab Clin Med. 1983 Feb;101(2):327-34
references.pmid: 6337226
references.citation: Science. 2002 Mar 29;295(5564):2387-92
references.pmid: 11923519
references.citation: Expert Rev Mol Med. 2008 Nov 04;10:e32
references.pmid: 18980707
references.citation: J Immunol. 2008 Aug 15;181(4):2753-63
references.pmid: 18684966
references.citation: J Immunol. 2009 Apr 1;182(7):4357-67
references.pmid: 19299736
references.citation: PLoS One. 2007 Nov 07;2(11):e1153
references.pmid: 17987129
references.citation: Nat Rev Immunol. 2005 Apr;5(4):331-42
references.pmid: 15803152
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Jul;293(1):L96-L104
references.pmid: 17384080
references.citation: Paediatr Respir Rev. 2000 Jun;1(2):101-6
references.pmid: 12531101
references.citation: Mol Med. 2006 Apr-Jun;12(4-6):105-14
references.pmid: 16953558
references.citation: Am J Pathol. 2008 Jul;173(1):144-53
references.pmid: 18556780
references.citation: Am J Respir Crit Care Med. 2008 Oct 15;178(8):822-31
references.pmid: 18658107
references.citation: J Immunol. 2005 Feb 1;174(3):1638-46
references.pmid: 15661927
references.citation: Clin Chim Acta. 2007 Feb;377(1-2):50-61
references.pmid: 17034776
references.citation: J Immunol. 2008 Apr 15;180(8):5662-9
references.pmid: 18390751
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3599-604
references.pmid: 15738423
references.citation: J Clin Invest. 1994 Feb;93(2):737-49
references.pmid: 7509347
references.citation: J Immunol. 2007 Jan 15;178(2):1013-20
references.pmid: 17202364
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 May;288(5):L958-65
references.pmid: 15640285
references.citation: N Engl J Med. 2005 May 12;352(19):1992-2001
references.pmid: 15888700
references.citation: Eur Respir J. 2004 Jan;23(1):146-58
references.pmid: 14738247
references.citation: Invest Ophthalmol Vis Sci. 1998 Aug;39(9):1744-50
references.pmid: 9699566
references.citation: FASEB J. 2008 Sep;22(9):3403-8
references.pmid: 18556462
references.citation: Nat Immunol. 2007 May;8(5):487-96
references.pmid: 17417641
references.citation: Ann Rheum Dis. 2008 May;67(5):727-8
references.pmid: 18408114
references.citation: Exp Lung Res. 1988;14(4):549-63
references.pmid: 3208719
references.citation: EMBO Rep. 2002 Oct;3(10):995-1001
references.pmid: 12231511
references.citation: Am J Respir Cell Mol Biol. 1989 Dec;1(6):479-87
references.pmid: 2561590
references.citation: Pediatr Pulmonol. 1997 Aug;24(2):137-42; discussion 159-61
references.pmid: 9292910
references.citation: Cornea. 2000 May;19(3):384-9
references.pmid: 10832704
references.citation: Pediatr Rev. 2001 Aug;22(8):257-64
references.pmid: 11483851
references.citation: Invest Ophthalmol Vis Sci. 1995 Jun;36(7):1306-16
references.pmid: 7775108
references.citation: Arthritis Rheum. 2003 Jul;48(7):2052-8
references.pmid: 12847700
references.citation: J Exp Med. 1976 Jun 1;143(6):1299-307
references.pmid: 1271012
references.citation: Am J Respir Cell Mol Biol. 2009 Dec;41(6):651-60
references.pmid: 19265175
references.citation: Am J Physiol Cell Physiol. 2006 Dec;291(6):C1318-25
references.pmid: 16855214
references.citation: Nat Med. 2004 May;10(5):487-93
references.pmid: 15077107
references.citation: PLoS One. 2009;4(2):e4664
references.pmid: 19247502
references.citation: Nat Med. 2006 Mar;12(3):317-23
references.pmid: 16474398
references.citation: Respir Res. 2008 May 01;9:39
references.pmid: 18447956
references.citation: Am J Respir Crit Care Med. 2006 Aug 15;174(4):400-7
references.pmid: 16728713
references.citation: EMBO J. 2003 Oct 15;22(20):5551-60
references.pmid: 14532127
references.citation: J Immunol. 2008 Sep 15;181(6):4240-6
references.pmid: 18768881