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.

Keywords

interleukin-4 / cytokine-induced neutrophil chemoattractants / intercellular adhesion molecule-1 / rat

References

[1] KonOM, KayAB. T cells and chronic asthma. Int Arch Allergy Immunol, 1999, 118(2–4): 133-135

[2] KayAB. T lymphocytes and their products in atopic allergy and asthma. Int Arch Allergy Appl Immunol, 1991, 94(1–4): 189-193

[3] TaubeC, DakhamaA, GelfandEW. Insights into the pathogenesis of asthma utilizing murine models. Int Arch Allerg Immun, 2004, 135(2): 173-186

[4] ChatilaTA. Interleukin-4 receptor signaling pathways in asthma pathogenesis. Trends Mol Med, 2004, 10(10): 493-499

[5] SurS, CrottyTB, KephartGM, et al.. Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa? Am Rev Respir Dis, 1993, 148(3): 713-719

[6] NorzilaMZ, FakesK, HenryRL, et al.. Interleukin-8 secretion and neutrophil recruitment accompanies induced sputum eosinophil activation in children with acute asthma. Am J Respir Crit Care Med, 2000, 161(3Pt1): 769-774

[7] FahyJV, KimKW, LiuJ, et al.. Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J Allergy Clin Immunol, 1995, 95(4): 843-852

[8] LamblinC, GossetP, Tillie-LeblondI, et al.. Bronchial neutrophilia in patients with noninfectious status asthmaticus. Am J Respir Crit Care Med, 1998, 157(2): 394-402

[9] TurnerMO, HussackP, SearsMR, et al.. Exacerbations of asthma without sputum eosinophilia. Thorax, 1995, 50(10): 1057-1061

[10] MukaidaN, HaradaA, MatsushimaK. Interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1), chemokines essentially involved in inflammatory and immune reactions. Cytokine Growth Factor Rev, 1998, 9(1): 9-23

[11] WagnerJG, RothRA. Neutrophil migration mechanisms, with an emphasis on the pulmonary vasculature. Pharmacol Rev, 2000, 52(3): 349-374

[12] BratDJ, BellailAC, Van MeirEG. The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro Oncol, 2005, 7(2): 122-133

[13] LiA, DubeyS, VarneyML, et al.. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J Immunol, 2003, 170(6): 3369-3376

[14] LeeKS, JinSM, KimHJ, et al.. Matrix metalloproteinase inhibitor regulates inflammatory cell migration by reducing ICAM-1 and VCAM-1 expression in a murine model of toluene diisocyanate-induced asthma. J Allergy Clin Immunol, 2003, 111(6): 1278-1284

[15] GuedersMM, BalbinM, RocksN, et al.. Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation. J Immunol, 2005, 175(4): 2589-2597

[16] OhbayashiH. Matrix metalloproteinases in lung diseases. Curr Protein Pept Sci, 2002, 3(4): 409-421

[17] SuzukiR, MiyazakiY, TakagiK, et al.. Matrix metalloproteinases in the pathogenesis of asthma and COPD: Implications for therapy. Treat Respir Med, 2004, 3(1): 17-27

[18] NishinaK. Expression of CINC-2 is related to the state of differentiation of alveolar epithelial cells. Am J Respir Cell Mol Biol, 2005, 33(5): 505-512

[19] ShibataF, KatoH, KonishiK, et al.. Differential changes in the concentrations of cytokine induced neutrophil chemoattractant (CINC)-1 and CINC-2 in exudate during rat lipopolysaccharide-induced inflammation. Cytokine, 1996, 8(3): 222-226

[20] ShibataF. Identification of a common receptor for three types of rat cytokine-induced neutrophil chemoattractants (CINCs). Cytokine, 2000, 12(9): 1368-1373

[21] GreenCE, PearsonDN, CamphausenRT, et al.. Shear-dependent capping of L-selectin and P-selectin glycoprotein ligand 1 by E-selectin signals activation of high-avidity beta2-integrin on neutrophils. J Immunol, 2004, 172(12): 7780-7790

[22] McEverRP, ZhuC. A catch to integrin activation. Nat Immunol, 2007, 8(10): 1035-1037

[23] ChanSC, ShumDK, TipoeGL, et al.. Upregulation of ICAM-1 expression in bronchial epithelial cells by airway secretions in bronchiectasis. Respir Med, 2008, 102(2): 287-298

[24] StrizI, MioT, AdachiY, et al.. IL-4 induces ICAM-1 expression in human bronchial epithelial cells and potentiates TNF-alpha. Am J Physiol, 1999, 277(1Pt1): L58-L64

[25] HuangH, Lavoie-LamoureuxA, MoranK, et al.. IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric oxide synthase mRNA by equine pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol, 2007, 292(5): L1147-L1154

[26] YangDF, HuangH, GuanS, et al.. Interleukin(IL)-4 promotion of CXCL-8 gene transcription is mediated by ERK1/2 pathway in human pulmonary artery endothelial cells. Mol Immunol, 2011, 48(15–16): 1784-1792

[27] ZhangC, GeCL, GuoRX, et al.. Effect of IL-4 on altered expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis. World J Gastroenterol, 2005, 11(43): 6770-6774

[28] RatthéC, EnnaciriJ, Garcês GonçalvesDM, et al.. Interleukin (IL)-4 induces leukocyte infiltration in vivo by an indirect mechanism. Mediators Inflamm, 2009, 2009: 1-10

[29] KangJL, LeeHW, LeeHS, et al.. Genistein prevents nuclear factor-kappa B activation and acute lung injury induced by lipopolysaccharide. Am J Respir Crit Care Med, 2001, 164(12): 2206-2212

[30] RabbHA, OlivensteinR, IssekutzTB, et al.. The role of the leukocyte adhesion molecules VLA-4, LFA-1, and MAC-1 in allergic airway responses in the rat. Am J Respir Crit Care Med, 1994, 149(5): 1186-1191

[31] LivakK. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods, 2001, 25(4): 402-408

[32] NiiroH, OtsukaT, IzuharaK, et al.. Regulation by interleukin-10 and interleukin-4 of cyclooxygenase-2 expression in human neutrophils. Blood, 1997, 89(5): 1621-1628

[33] MarieC, PittonC, FittingC, et al.. IL-10 and IL-4 synergize with TNF-alpha to induce IL-1ra production by human neutrophils. Cytokine, 1996, 8(2): 147-151

[34] ColottaF, ReF, MuzioM, et al.. Interleukin-1 type II receptor: A decoy target for IL-1 that is regulated by IL-4. Science, 1993, 261(5120): 472-475

[35] MasinovskyB, UrdalD, GallatinWM. IL-4 acts synergistically with IL-1 beta to promote lymphocyte adhesion to microvascular endothelium by induction of vascular cell adhesion molecule-1. J Immunol, 1990, 145(9): 2886-2895

[36] DuboisGR, BruijnzeelPL. IL-4-induced migration of eosinophils in allergic inflammation. Ann N Y Acad Sci, 1994, 725: 268-273

[37] HiesterAA, MetcalfDR, CampbellPA. Interleukin-4 is chemotactic for mouse macrophages. Cell Immunol, 1992, 139(1): 72-80

[38] ClinchyB, ElenstromC, SeverinsonE, et al.. T and B cell collaboration: Induction of motility in small, resting B cells by interleukin 4. Eur J Immunol, 1991, 21(6): 1445-1451

[39] BoeyH, RosenbaumR, CastracaneJ, et al.. Interleukin-4 is a neutrophil activator. J Allergy Clin Immunol, 1989, 83(5): 978-984

[40] Lavoie-LamoureuxA, MoranK, BeauchampG, et al.. IL-4 activates equine neutrophils and induces a mixed inflammatory cytokine expression profile with enhanced neutrophil chemotactic mediator release ex vivo. Am J Physiol Lung Cell Mol Physiol, 2010, 299(4): L472-L482

[41] MulliganMS, JonesML, VaporciyanAA, et al.. Protective effects of IL-4 and IL-10 against immune complex-induced lung injury. J Immunol, 1993, 151(10): 5666-5674

[42] PerrettiM, SzaboC, ThiemermannC. Effect of inter leukin-4 and interleukin-10 on leucocyte migration and nitric oxide production in the mouse. Br J Pharmacol, 1995, 116(4): 2251-2257

[43] Piela-SmithTH, BroketaG, HandA, et al.. Regulation of ICAM-1 expression and function in human dermal fibroblasts by IL-4. J Immunol, 1992, 148(5): 1375-1381

[44] ObiriNI, TandonN, PuriRK. Up-regulation of intercellular adhesion molecule 1 (ICAM-1) on human renal cell carcinoma cells by interleukin-4. Int J Cancer, 1995, 61(5): 635-642

[45] ValentP, BevecD, MaurerD, et al.. Interleukin 4 promotes expression of mast cell ICAM-1 antigen. Proc Natl Acad Sci USA, 1991, 88(8): 3339-3342

[46] ChinenLT, CiprianoIM, de OliveiraRS, et al.. Recombinant interleukin-4-treated macrophages, epithelioid cell surrogates, harbor and arrest mycobacterium avium multiplication in vitro. Microbes Infect, 2006, 8(4): 965-973

[47] BergerRB, BlackwellNM, LassJH, et al.. IL-4 and IL-13 regulation of ICAM-1 expression and eosinophil recruitment in onchocerca volvulus keratitis. Invest Ophthalmol Vis Sci, 2002, 43(9): 2992-2997

[48] SpoelstraFM, PostmaDS, HovengaH, et al.. Interferon-gamma and interleukin-4 differentially regulate ICAM-1 and VCAM-1 expression on human lung fibroblasts. Eur Respir J, 1999, 14(4): 759-766

[49] VignolaAM, BonsignoreG, SienaL, et al.. ICAM-1 and alpha3beta1 expression by bronchial epithelial cells and their in vitro modulation by inflammatory and anti-inflammatory mediators. Allergy, 2000, 55(10): 931-939

[50] JatakanonA, UasufC, MaziakW, et al.. Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med, 1999, 160(5Pt1): 1532-1539

[51] YousefiS, HemmannS, WeberM, et al.. IL-8 is expressed by human peripheral blood eosinophils. Evidence for increased secretion in asthma. J Immunol, 1995, 154(10): 5481-5490

[52] ShannonJ, ErnstP, YamauchiY, et al.. Differences in airway cytokine profile in severe asthma compared to moderate asthma. Chest, 2008, 133(2): 420-426

[53] ZerfaouiM, NauraAS, ErramiY, et al.. Effects of PARP-1 deficiency on airway inflammatory cell recruitment in response to LPS or TNF: Differential effects on CXCR2 ligands and duffy antigen receptor for chemokines. J Leukoc Biol, 2009, 86(6): 1385-1392

[54] GjelstrupLC, BoesenT, KragstrupTW, et al.. Shedding of large functionally active CD11/CD18 integrin complexes from leukocyte membranes during synovial inflammation distinguishes three types of arthritis through differential epitope exposure. J Immunol, 2010, 185(7): 4154-4168

[55] ManiconeAM. Role of the pulmonary epithelium and inflammatory signals in acute lung injury. Expert Rev Clin Immunol, 2009, 5(1): 63-75

[56] NathanC. Neutrophils and immunity: Challenges and opportunities. Nat Rev Immunol, 2006, 6(3): 173-182

[57] YamasawaH, IshiiY, KitamuraS. Cytokine-induced neutrophil chemoattractant in a rat model of lipopolysaccharide-induced acute lung injury. Inflammation, 1999, 23(3): 263-274

[58] HaddadelB, McCluskieK, BirrellMA, et al.. Differential effects of ebselen on neutrophil recruitment, chemokine, and inflammatory mediator expression in a rat model of lipopolysaccharide-induced pulmonary inflammation. J Immunol, 2002, 169(2): 974-982

[59] ZhaoM, BrownDM, MaccallumJ, et al.. Effect of nippostrongylus brasiliensis L3ES on inflammatory mediator gene transcription in lipopolysaccharide lung inflammation. Parasite Immunol, 2009, 31(1): 50-56

[60] Mafra de LimaF, VillaverdeAB, SalgadoMA, et al.. Low intensity laser therapy (LILT) in vivo acts on the neutrophils recruitment and chemokines/cytokines levels in a model of acute pulmonary inflammation induced by aerosol of lipopolysaccharide from escherichia coli in rat. J Photochem Photobiol B, 2010, 101(3): 271-278

[61] MartinsJO, ZanoniFL, MartinsDO, et al.. Insulin regulates cytokines and intercellular adhesion molecule-1 gene expression through nuclear factor-kappa B activation in LPS-induced acute lung injury in rats. Shock, 2009, 31(4): 404-409