title: Interleukin (IL)-4 induces production of cytokine-induced neutrophil chemoattractants (CINCs) and intercellular adhesion molecule (ICAM)-1 in lungs of asthmatic rats.
abstract: The present study aimed to examine the effect of interleukin (IL)-4 on neutrophil chemotaxis in airway inflammation in asthmatic rats and the possible mechanism. Male Wistar rats were intranasally instilled with recombinant rat (rr) IL-4 (rrIL-4) at different doses [2, 4 or 8 μg/animal, dissolved in 200 μL normal saline (NS)] or rrIL-4 at 4 μg/animal (dissolved in 200 μL NS). NS (200 μL) and LPS (6 mg/kg/animal, dissolved in 200 μL NS) were intranasally given respectively in the negative and positive control groups. Moreover, the asthmatic lung inflammation was induced in rats which were then intranasally treated with rrIL-4 (4 μg/animal) or LPS (6 mg/kg/animal). The normal rats treated with different doses of rrIL-4 and those asthmatic rats were sacrificed 6 h later. And animals instilled with rrIL-4 at 4 μg were sacrificed 6, 12 or 24 h later. The bronchoalveolar lavage fluid (BALF) and lungs were harvested for detection of leukocyte counts by Wright-Giemsa staining and lung histopathology by haematoxylin-eosin (HE) staining. The levels of cytokine-induced neutrophil chemoattractant (CINC)-1 and intercellular adhesion molecule (ICAM)-1 in BALF were determined by ELISA. Real-time PCR was used to measure the mRNA expression of CINCs (CINC-1, CINC-2α, CINC-2β, CINC-3) and ICAM-1 in lung tissues. The results showed that the intranasal instillation of IL-4 did not induce a recruitment of neutrophils in BALF in rats. However, IL-4 could increase the CINC-1 level in BALF in a dose-dependent manner at 6 h. But the mRNA expression levels of CINC-1, CINC-2α, CINC-2β, CINC-3 were not significantly increased in lungs of IL-4-treated rats relative to NS negative control group. Moreover, IL-4 was found to augment the mRNA expression of ICAM-1 in lungs and the ICAM-1 level in BALF at 6 h. However, the increase in CINC-1 and ICAM-1 levels in BALF of IL-4-treated asthmatic rats was not significantly different from that in untreated asthmatic rats. These findings indicate that IL-4 does not directly recruit neutrophils in the rat lungs, but it may contribute to airway neutrophilia through up-regulation of CINC-1 and ICAM-1.
authors.affiliation: Department of Respiratory Diseases and Critical Care Medicine, Tongji Hospital, Tonji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Respiratory Diseases and Critical Care Medicine, Henan Provincial People's Hospital, Zhengzhou, 450003, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Guo
authors.affiliation: Department of Respiratory Diseases and Critical Care Medicine, Tongji Hospital, Tonji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. hhongtj@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Da-Xiong
authors.initials: DX
authors.lastname: Zeng
authors.affiliation: Department of Respiratory Diseases and Critical Care Medicine, Tongji Hospital, Tonji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Diseases and Critical Care Medicine, Tongji Hospital, Tonji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Fang
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, J2S 7C6, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lavoie
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D002630:Chemotactic Factors / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002630:Chemotactic Factors; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4
references.citation: Expert Rev Clin Immunol. 2009 Jan 1;5(1):63-75
references.pmid: 19885383
references.citation: Cytokine Growth Factor Rev. 1998 Mar;9(1):9-23
references.pmid: 9720753
references.citation: J Allergy Clin Immunol. 1989 May;83(5):978-84
references.pmid: 2541192
references.citation: Int Arch Allergy Immunol. 2004 Oct;135(2):173-86
references.pmid: 15375327
references.citation: J Immunol. 1993 Nov 15;151(10):5666-74
references.pmid: 7901280
references.citation: Cell Immunol. 1992 Jan;139(1):72-80
references.pmid: 1530834
references.citation: J Immunol. 1992 Mar 1;148(5):1375-81
references.pmid: 1347050
references.citation: Cytokine. 1996 Feb;8(2):147-51
references.pmid: 8777273
references.citation: J Allergy Clin Immunol. 2003 Jun;111(6):1278-84
references.pmid: 12789230
references.citation: J Immunol. 2005 Aug 15;175(4):2589-97
references.pmid: 16081833
references.citation: Trends Mol Med. 2004 Oct;10(10):493-9
references.pmid: 15464449
references.citation: Shock. 2009 Apr;31(4):404-9
references.pmid: 18791499
references.citation: Nat Rev Immunol. 2006 Mar;6(3):173-82
references.pmid: 16498448
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 May;292(5):L1147-54
references.pmid: 17494951
references.citation: Am Rev Respir Dis. 1993 Sep;148(3):713-9
references.pmid: 8368644
references.citation: Blood. 1997 Mar 1;89(5):1621-8
references.pmid: 9057644
references.citation: Br J Pharmacol. 1995 Oct;116(4):2251-7
references.pmid: 8564256
references.citation: Thorax. 1995 Oct;50(10):1057-61
references.pmid: 7491553
references.citation: Am J Respir Crit Care Med. 1998 Feb;157(2):394-402
references.pmid: 9476849
references.citation: Mediators Inflamm. 2009;2009:193970
references.pmid: 19753321
references.citation: Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):133-5
references.pmid: 10224360
references.citation: Am J Respir Cell Mol Biol. 2005 Nov;33(5):505-12
references.pmid: 16055671
references.citation: J Immunol. 2010 Oct 1;185(7):4154-68
references.pmid: 20826754
references.citation: Cytokine. 1996 Mar;8(3):222-6
references.pmid: 8833037
references.citation: Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3339-42
references.pmid: 1673030
references.citation: J Immunol. 2004 Jun 15;172(12):7780-90
references.pmid: 15187162
references.citation: Mol Immunol. 2011 Sep;48(15-16):1784-92
references.pmid: 21645924
references.citation: J Allergy Clin Immunol. 1995 Apr;95(4):843-52
references.pmid: 7722165
references.citation: Treat Respir Med. 2004;3(1):17-27
references.pmid: 15174890
references.citation: J Immunol. 1995 May 15;154(10):5481-90
references.pmid: 7730650
references.citation: J Immunol. 2003 Mar 15;170(6):3369-76
references.pmid: 12626597
references.citation: Microbes Infect. 2006 Apr;8(4):965-73
references.pmid: 16515875
references.citation: J Immunol. 2002 Jul 15;169(2):974-82
references.pmid: 12097404
references.citation: Chest. 2008 Feb;133(2):420-6
references.pmid: 18071017
references.citation: Respir Med. 2008 Feb;102(2):287-98
references.pmid: 17931847
references.citation: Am J Respir Crit Care Med. 2001 Dec 15;164(12):2206-12
references.pmid: 11751189
references.citation: Curr Protein Pept Sci. 2002 Aug;3(4):409-21
references.pmid: 12370004
references.citation: Int Arch Allergy Appl Immunol. 1991;94(1-4):189-93
references.pmid: 1937873
references.citation: Am J Physiol Lung Cell Mol Physiol. 2010 Oct;299(4):L472-82
references.pmid: 20639353
references.citation: Pharmacol Rev. 2000 Sep;52(3):349-74
references.pmid: 10977867
references.citation: Invest Ophthalmol Vis Sci. 2002 Sep;43(9):2992-7
references.pmid: 12202520
references.citation: Parasite Immunol. 2009 Jan;31(1):50-6
references.pmid: 19121083
references.citation: World J Gastroenterol. 2005 Nov 21;11(43):6770-4
references.pmid: 16425382
references.citation: Neuro Oncol. 2005 Apr;7(2):122-33
references.pmid: 15831231
references.citation: Am J Physiol. 1999 Jul;277(1):L58-64
references.pmid: 10409231
references.citation: Ann N Y Acad Sci. 1994 May 28;725:268-73
references.pmid: 8030998
references.citation: Science. 1993 Jul 23;261(5120):472-5
references.pmid: 8332913
references.citation: Eur Respir J. 1999 Oct;14(4):759-66
references.pmid: 10573217
references.citation: Nat Immunol. 2007 Oct;8(10):1035-7
references.pmid: 17878912
references.citation: Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1532-9
references.pmid: 10556116
references.citation: Am J Respir Crit Care Med. 1994 May;149(5):1186-91
references.pmid: 8173758
references.citation: Inflammation. 1999 Jun;23(3):263-74
references.pmid: 10392760
references.citation: J Leukoc Biol. 2009 Dec;86(6):1385-92
references.pmid: 19741160
references.citation: J Immunol. 1990 Nov 1;145(9):2886-95
references.pmid: 1698865
references.citation: Allergy. 2000 Oct;55(10):931-9
references.pmid: 11030373
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Cytokine. 2000 Sep;12(9):1368-73
references.pmid: 10975996
references.citation: Int J Cancer. 1995 May 29;61(5):635-42
references.pmid: 7768636
references.citation: Eur J Immunol. 1991 Jun;21(6):1445-51
references.pmid: 2044655
references.citation: J Photochem Photobiol B. 2010 Dec 2;101(3):271-8
references.pmid: 20728373
references.citation: Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):769-74
references.pmid: 10712320