title: Role of interleukin-1 and MyD88-dependent signaling in rhinovirus infection.
abstract: Rhinoviral infection is an important trigger of acute inflammatory exacerbations in patients with underlying airway disease. We have previously established that interleukin-1β (IL-1β) is central in the communication between epithelial cells and monocytes during the initiation of inflammation. In this study we explored the roles of IL-1β and its signaling pathways in the responses of airway cells to rhinovirus-1B (RV-1B) and further determined how responses to RV-1B were modified in a model of bacterial coinfection. Our results revealed that IL-1β dramatically potentiated RV-1B-induced proinflammatory responses, and while monocytes did not directly amplify responses to RV-1B alone, they played an important role in the responses observed with our coinfection model. MyD88 is the essential signaling adapter for IL-1β and most Toll-like receptors. To examine the role of MyD88 in more detail, we created stable MyD88 knockdown epithelial cells using short hairpin RNA (shRNA) targeted to MyD88. We determined that IL-1β/MyD88 plays a role in regulating RV-1B replication and the inflammatory response to viral infection of airway cells. These results identify central roles for IL-1β and its signaling pathways in the production of CXCL8, a potent neutrophil chemoattractant, in viral infection. Thus, IL-1β is a viable target for controlling the neutrophilia that is often found in inflammatory airway disease and is exacerbated by viral infection of the airways.
authors: Academic Unit of Respiratory Medicine, School of Medicine and Biomedical Sciences, University of Sheffield, L Floor, Royal Hallamshire Hospital, Sheffield S10 2JF, United Kingdom.
authors: Clare A
authors: CA
authors: Stokes
authors: Saila
authors: S
authors: Ismail
authors: Emily P
authors: EP
authors: Dick
authors: Julie A
authors: JA
authors: Bennett
authors: Sebastian L
authors: SL
authors: Johnston
authors: Michael R
authors: MR
authors: Edwards
authors: Ian
authors: I
authors: Sabroe
authors: Lisa C
authors: LC
authors: Parker
references: J Infect Dis. 2003 Dec 15;188(12):1928-39
references: 14673774
references: Am J Physiol Lung Cell Mol Physiol. 2000 Jun;278(6):L1146-53
references: 10835319
references: Am J Respir Crit Care Med. 1999 Jul;160(1):100-8
references: 10390386
references: J Immunol. 1996 Jan 15;156(2):621-7
references: 8543813
references: Int Immunol. 2009 Apr;21(4):317-37
references: 19246554
references: PLoS Pathog. 2010 Nov 04;6(11):e1001178
references: 21079690
references: J Biol Chem. 1999 Apr 2;274(14):9707-20
references: 10092659
references: Hum Immunol. 2007 Aug;68(8):675-80
references: 17678722
references: Clin Rev Allergy Immunol. 2003 Feb;24(1):85-110
references: 12644720
references: J Clin Invest. 1999 Oct;104(7):957-65
references: 10510336
references: Am J Respir Crit Care Med. 2007 Feb 15;175(4):306-11
references: 17138954
references: J Immunol. 2005 Jun 15;174(12):8056-63
references: 15944313
references: FASEB J. 2006 Oct;20(12):2153-5
references: 16935934
references: Chest. 2006 Feb;129(2):317-324
references: 16478847
references: Laryngoscope. 2009 Jul;119(7):1406-11
references: 19434681
references: Thorax. 2007 Aug;62(8):733-8
references: 17687100
references: Am J Physiol Lung Cell Mol Physiol. 2010 Aug;299(2):L263-71
references: 20435687
references: Respir Med. 2008 Sep;102(9):1311-20
references: 18579366
references: Nat Med. 2006 Sep;12(9):1023-6
references: 16906156
references: Chest. 2005 Aug;128(2):1072-3; author reply 1073
references: 16100218
references: Microbes Infect. 2006 Mar;8(3):758-66
references: 16513395
references: Am J Respir Cell Mol Biol. 2010 Oct;43(4):413-21
references: 19880820
references: J Immunol. 2008 Oct 15;181(8):5606-17
references: 18832719
references: Clin Exp Allergy. 2003 Oct;33(10):1415-8
references: 14519149
references: Am J Respir Crit Care Med. 2010 May 1;181(9):917-27
references: 20133931
references: FASEB J. 2006 Oct;20(12):2121-3
references: 16914605
references: J Immunol. 2011 Feb 15;186(4):2514-22
references: 21248248
references: Pediatr Infect Dis J. 2009 Apr;28(4):337-9
references: 19258921
references: Am J Respir Crit Care Med. 2001 Feb;163(2):349-55
references: 11179105
references: Acta Anaesthesiol Scand. 2002 Sep;46(8):959-64
references: 12190796
references: Immunology. 2009 Sep;128(1):58-68
references: 19689736
references: Am J Respir Crit Care Med. 2005 Apr 15;171(8):814-22
references: 15657467
references: J Virol. 2006 Aug;80(16):8248-58
references: 16873280
references: Allergy Asthma Proc. 2008 Sep-Oct;29(5):468-74
references: 18926055
references: J Immunol. 2004 Apr 15;172(8):4977-86
references: 15067079
references: Thorax. 2008 Jun;63(6):519-25
references: 18245149
references: Clin Exp Allergy. 2010 Aug;40(8):1203-13
references: 20545701
references: Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 1):1185-90
references: 10764310
references: Cancer Res. 1988 Apr 1;48(7):1904-9
references: 2450641
references: J Leukoc Biol. 2006 Dec;80(6):1364-74
references: 17020930
references: Am J Respir Cell Mol Biol. 1999 Jun;20(6):1220-8
references: 10340941
references: Am J Physiol. 1997 Oct;273(4):L749-59
references: 9357849
references: Cell Immunol. 2003 Jan;221(1):37-41
references: 12742380
references: Cytokine Growth Factor Rev. 2003 Jun-Aug;14(3-4):193-209
references: 12787559
references: Am J Physiol Lung Cell Mol Physiol. 2007 Oct;293(4):L1021-8
references: 17631613
references: Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2574-9
references: 20133797
references: Am J Respir Cell Mol Biol. 2006 Aug;35(2):227-35
references: 16543608
references: J Immunol. 2000 Apr 15;164(8):4185-96
references: 10754314
references: J Virol Methods. 2011 Jan;171(1):212-8
references: 21070809
references: Nat Med. 2007 Jul;13(7):851-6
references: 17572686
references: J Clin Microbiol. 2007 Nov;45(11):3655-64
references: 17804649
references: Eur Respir J. 1994 Jun;7(6):1096-102
references: 7925879
references: J Infect Dis. 1997 Feb;175(2):323-9
references: 9203653
references: Am J Respir Cell Mol Biol. 2000 Oct;23(4):530-6
references: 11017919
references: Annu Rev Immunol. 2010;28:367-88
references: 20192808
references: J Virol. 2002 Jan;76(1):427-31
references: 11739709
references: In Vitro Cell Dev Biol Anim. 1995 Nov;31(10):738-40
references: 8564059
references: Immunology. 2009 Jun;127(2):249-55
references: 19175800
references: Eur Respir J Suppl. 2001 Dec;34:50s-59s
references: 12392035
references: J Immunol. 2009 Dec 1;183(11):6989-97
references: 19890046
references: Allergy. 2009 Mar;64(3):375-86
references: 19175599
references: J Leukoc Biol. 2004 Aug;76(2):441-50
references: 15155777
references: Am J Respir Crit Care Med. 1999 Feb;159(2):487-94
references: 9927362
references: Proc Am Thorac Soc. 2005;2(2):150-6
references: 16113484
references: J Exp Med. 2005 Mar 21;201(6):937-47
references: 15781584
references: Annu Rev Immunol. 2009;27:519-50
references: 19302047
references: Am J Physiol. 1999 Jul;277(1):L13-21
references: 10409226
references: Infect Immun. 2005 Nov;73(11):7151-60
references: 16239509
references: J Immunol. 1998 Jun 15;160(12):6172-81
references: 9637536