Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

Respiratory Research

J Margaret Hughes¹  Carol L Armour³  Janette K Burgess²  Daniel J Lalor¹  Hatem Alkhouri¹  Petra Seidel¹ 

[1]Respiratory Research Group, Faculty of Pharmacy, The University of Sydney, A15, Science Rd, Sydney, NSW 2006, Australia

[2]Woolcock Institute of Medical Research, Sydney, NSW Australia

[3]Current affiliation: Discipline of Pharmacology, The University of Sydney and Woolcock Institute of Medical Research, Sydney, NSW Australia

关键词: Rosiglitazone;    Ciglitazone;    Fluticasone;    Salmeterol;    Long-acting β2-agonists;    Glucocorticoids;    Mast cell chemoattractant;   

Others  :  796635
DOI  :  10.1186/1465-9921-13-90

 received in 2012-03-26, accepted in 2012-09-27,  发布年份 2012

【 摘 要 】

Background

Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro.

Methods

Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher’s post-hoc test.

Results

Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix). The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM) inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production.

Conclusions

Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

【 授权许可】

   
2012 Seidel et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Fabbri L, Peters SP, Pavord I, Wenzel SE, Lazarus SC, Macnee W, Lemaire F, Abraham E: Allergic rhinitis, asthma, airway biology, and chronic obstructive pulmonary disease in AJRCCM in 2004. Am J Respir Crit Care Med 2005, 171:686-698.
• [2]Carroll NG, Mutavdzic S, James AL: Distribution and degranulation of airway mast cells in normal and asthmatic subjects. Eur Respir J 2002, 19:879-885.
• [3]Begueret H, Berger P, Vernejoux JM, Dubuisson L, Marthan R, Tunon-de-Lara JM: Inflammation of bronchial smooth muscle in allergic asthma. Thorax 2007, 62:8-15.
• [4]Brightling CE, Bradding P, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID: Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med 2002, 346:1699-1705.
• [5]Berger P, Girodet PO, Begueret H, Ousova O, Perng DW, Marthan R, Walss AF, Tunon deLara JM: Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis. FASEB J 2003, 17:2139-2141.
• [6]Sukkar MB, Issa R, Xie S, Olymanns U, Newton R, Chung KF: Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids. Am J Physiol Lung Cell Mol Physiol 2003, 287:L1230-L1240.
• [7]Hollins F, Kaur D, Yang W, Cruse G, Saunders R, Sutcliffe A, Berger P, Brightling CE, Bradding P: Human airway smooth muscle promotes human lung mast cell survival, proliferation and constitutive activation: cooperative roles for CADM1, stem cell factor and IL-6. J Immunol 2008, 181:2772-2780.
• [8]Brightling CE, Ammit AJ, Kaur D, Black JL, Wardlaw AJ, Hughes JM, Bradding P: The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle. Am J Respir Crit Care Med 2005, 171:1103-1108.
• [9]Alrashdan Y, Alkhouri H, Chen E, Lalor DJ, Poniris M, Henness S, Brightling CE, Burgess JK, Armour CL, Ammit AJ, Hughes JM: Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement. Am J Physiol Lung Cell Mol Physiol 2012., 302
• [10]Pang L, Knox AJ: Synergistic inhibition by beta(2)-agonists and corticosteroids on tumor necrosis factor-alpha-induced interleukin-8 release from cultured human airway smooth-muscle cells. Am J Respir Cell Mol Biol 2000, 23:79-85.
• [11]Nie M, Knox AJ, Pang L: Beta2-Adrenoceptor agonists, like glucocorticoids, repress eotaxin gene transcription by selective inhibition of histone H4 acetylation. J Immunol 2005, 175:478-486.
• [12]Ammit AJ, Lazaar AL, Irani C, O'Neill GM, Gordon ND, Amrani Y, Penn RB, Panettieri RA Jr: Tumor necrosis factor-alpha-induced secretion of RANTES and interleukin-6 from human airway smooth muscle cells: modulation by glucocorticoids and beta-agonists. Am J Respir Cell Mol Biol 2002, 26:465-474.
• [13]Clarke DL, Clifford RL, Jindarat S, Proud D, Pang L, Belvisi M, Knox AJ: TNFα and IFNγ synergistically enhance transcriptional activation of CXCL10 in human airway smooth muscle cells via STAT-1, NF-κB, and the transcriptional coactivator CREB-binding protein. J Biol Chem 2010, 17(285):29101-29110.
• [14]Adcock IM, Caramori G, Chung KF: New targets for drug development in asthma. Lancet 2008, 372:1073-1087.
• [15]Nie M, Corbett L, Knox A, Pang L: Differential regulation of chemokine expression by peroxisome proliferator-activated receptor gamma agonists:interactions with glucocorticoids and beta2-agonists. J Biol Chem 2005, 280:2550-2561.
• [16]Benayoun L, Letuve S, Druilhe A, Boczkowski J, Dombret MC, Mechighel P, Megret J, Leseche G, Aubier M, Pretolani M: Regulation of peroxisome proliferator-activated receptor gamma expression in human asthmatic airways: relationaship with proliferation, apoptosis, and airway remodelling. Am J Respir Crit Care Med 2001, 164:1487-1494.
• [17]Park SJ, Lee KS, Min KH, Choe YH, Moon H, Chae HJ, Yoo WH, Lee YC: Peroxisome proliferator-activated receptor gamma agonist down-regulates IL17 expression in a murine model of allergic airway inflammation. J Immunol 2009, 183:3259-3267.
• [18]Ward JE, Gould H, Harris T, Bonacci JV, Stewart AG: PPAR gamma ligands, 15-deoxy-delta12,14-prostaglandin J2 and rosiglitazone regulate human cultured airway smooth muscle proliferation through different mechanisms. Br J Pharmacol 2004, 141:517-525.
• [19]Collino M, Aragno M, Mastrocola R, Gallicchio M, Rosa AC, Dianzani C, Danni O, Thiemermann C, Fantozzi R: Modulation of the oxidative stress and inflammatory response by PPAR-gamma agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion. Eur J Pharmacol 2006, 530:70-80.
• [20]Zhang HL, Xu M, Wei C, Qin AP, Liu CF, Hong LZ, Zhao XY, Liu J, Qin ZH: Neuroprotective effects of pioglitazone in a rat model of permanent focal cerebral ischemia are associated with peroxisome proliferators-activated receptor gamma-mediated suppression of nuclear factor-kB signalling pathway. Neuroscience 2011, 176:381-395.
• [21]Hammad H, de Heer HJ, Soullie T, Angeli V, Trottein F, Hoogsteden HC, Lambrecht BN: Activation of peroxisome proliferator-activated receptor-gamma in dendritic cells inhibits the development of eosinophilic airway inflammation in a mouse model of asthma. Am J Pathol 2004, 164:263-271.
• [22]Trifilieff A, Bench A, Hanley M, Bayley D, Campbell E, Whittaker P: PPAR-alpha and -gamma but not -delta agonists inhibit airway inflammation in a murine model of asthma: in vitro evidence for an NF-kappaB-independent effect. Br J Pharmacol 2003, 139:163-171.
• [23]Zhu M, Flynt L, Ghosh S, Mellema M, Bannerjee A, Williams E, Panettieri RA, Shore SA: Anti-inflammatory effects of thiazolidinediones in human airway smooth muscle cells. Am J Respir Cell Mol Biol 2011, 45:111-119.
• [24]Baraket M, Oliver BGG, Burgess JK, Lim S, King GC, Black JL: Is low dose inhaled corticosteroid therapy as effective for inflammation and remodelling in asthma? A randomized parallel group study. Respir Res 2012, 13:11. BioMed Central Full Text
• [25]Ko FWS, Diba C, Roth M, McKay K, Johnson PR, Salome C, King GG: A comparison of airway and serum matrix metalloproteinase-9 activity among normal subjects, asthmatic patients, and patients with mucus hypersecretion. Chest 2005, 127:1919-1927.
• [26]Johnson PR, Roth M, Tamm M, Hughes M, Ge Q, King G, Burgess JK, Black JL: Airway smooth muscle cell proliferation is increased in asthma. Am J Respir Crit Care Med 2001, 164:474-477.
• [27]Tanaka Y, Yamashita Y, Horinouchi T, Koike K: Adrenaline produces the relaxation of guinea-pig airway smooth muscle primarily through the mediation of β2-adrenoceptors. J Smooth Muscle Res 2005, 41:153-161.
• [28]Patel HJ, Belvisi MG, Bishop-Bailey D, Yacoub MH, Mitchell JA: Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior anti-inflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapy. J Immunol 2003, 170:2663-2669.
• [29]Tan X, Dagher H, Hutton CA, Bourke JE: Effects of PPAR gamma ligands on TGF-beta1-induced epithelial-mesenchymal transition in alveolar epithelial cells. Respir Res 2010, 11:21-34. BioMed Central Full Text
• [30]Edwards MR, Mukaida N, Johnson M, Johnston SL: IL-1beta induces IL-8 in bronchial cells via NF-kappaB and NF-IL6 transcription factors and can be suppressed by glucocorticoids. Pulm Pharmacol Ther 2005, 18:337-345.
• [31]Hardaker EL, Bacon AM, Carlson K, Roshak AK, Foley JJ, Schmidt DB, Buckley PT, Comegys M, Panettieri RA, Sarau HM, Belmonte KE: Regulation of TNF-{alpha}- and IFN-{gamma}-induced CXCL10 expression. FASEB J 2004, 18:191-193.
• [32]Reddy PJ, Aksoy MO, Yang Y, Li XX, Ji R, Kelsen SG: Inhibition by salmeterol and cilomilast of fluticasone-enhanced IP10 release in airway epithelial cells. COPD 2008, 5:5-11.
• [33]Banerjee A, Damera G, Bhandare R, Gu S, Lopez-Boado Y, Panettieri R Jr, Tliba O: Vitamin D and glucocorticoids differentially modulate chemokine expression in human airway smooth muscle cells. Br J Pharmacol 2008, 155:84-92.
• [34]Tliba O, Cidlowski JA, Amrani Y: CD38 expression is insensitive to steroid action in cells treated with tumor necrosis factor-alpha and interferon-gamma by a mechanism involving the up-regulation of the glucocorticoid receptor beta isoform. Mol Pharmacol 2006, 69:588-596.
• [35]Tliba O, Damera G, Banerjee A, Gu S, Baidouri H, Keslacy S, Amrani Y: Cytokines induce an early steroid resistance in airway smooth muscle cells: novel role of IRF-1. Am J Respir Cell Mol Biol 2008, 38:463-472.
• [36]Fukakusa M, Bergeron C, Tulic MK, Fiset M-O, Al Dewachi O, Laviolette M, Hamid Q, Chakir J: Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil, IL-8, and IFN-g-inducible protein expression in asthmatic airway mucosa. J Allergy Clin Immunol 2005, 115:280-286.
• [37]Anderson GP, Linden A, Rabe KF: Why are long acting beta-adrenoceptor agonists long-acting? Eur Respir J 1994, 7:569-578.
• [38]Coleman RA: On the mechanism of the persistent action of salmeterol: what is the current position? Brit J Pharmacol 2009, 158:180-182.
• [39]Cazzola M, Calzetta L, Matera MG: β2-adrenoceptor agonists: current and future direction. Br J Pharmacol 2011, 163:4-17.
• [40]Jack D: A way of looking at agonism and antagonism: lessons from salbutamol, salmeterol and other β2-adrenoceptor agonists. Br J clin Pharmac 1991, 31:501-514.
• [41]Freddolino PL, Kalani MYS, Vaidehi N, Floriano WB, Hall SE, Trabanino RJ, Kam VWT, Goddard WA: Predicted 3D structure for the human β2-adrenergic receptor and its binding site for agonists and antagonists. PNAS 2004, 101:2736-2741.
• [42]Holden NS, Rider CF, Bell MJ, Velayudhan J, King EM, Kaur M, Salmon M, Giembycz MA, Newton R: Enhancement of inflammatory mediator release by β2-adrenoceptor agonists in airway epithelial cells is reversed by glucocorticoid action. Br J Pharmacol 2010, 160:410-420.
• [43]Yeruva S, Ramadori G, Raddatz D: NF-kappaB-dependent synergistic regulation of CXCL10 gene expression by IL-1beta and IFN-gamma in human intestinal epithelial cell lines. Int J Colorectal Dis 2008, 23:305-317.
• [44]Mahn K, Hirst SJ, Ying S, Holt MR, Lavendar P, Ojo OO, Siew L, Simcock DE, McVicker CG, Kanabar V, Snetkov VA, O’Connor BJ, Karner C, Cousins DJ, Macedo P, Chung KF, Corrigan CJ, Ward JP, Lee TH: Diminished sarco/endoplasmic reticulum Ca2+ (SERCA) expression contributes to airway remodelling in bronchial asthma. Proc Natl Acad Sci USA 2009, 106:10775-10780.
• [45]Trian T, Bernard G, Begueret H, Rossignol R, Girodet PO, Ghosh D, Ousova O, Vernejoux JM, Marthan R, Tunn-de-Lara JM, Berger P: Bronchial smooth muscle remodelling involves calcium-dependent enhanced mitochondrial biogenesis in asthma. J Exp Med 2007, 204:3173-3181.
• [46]Amrani Y, Lazaar A, Hoffman R, Amin K, Ousmer S, Panettieri RA: Activation of p55 tumor necrosis factor-alpha receptor-1 coupled to tumor necrosis factor receptor-associated factor 2 stimulates intercellular adhesion molecule-1 expression by modulating a thapsigargin-sensitive pathway in human tracheal smooth muscle cells. Mol Pharmacol 2000, 58:237-245.
• [47]Trian T, Burgess JK, Niimi K, Moir LM, Ge Q, Berger P, Liggett SB, Black JL, Oliver BG: β2-agonist induced cAMP is decreased in asthmatic airway smooth muscle due to increased PDE4D. PLoS One 2011, 6(5):e20000.
• [48]Kassel KM, Wyatt TA, Panettiere RA, Toews ML: Inhibition of human airway smooth muscle cell proliferation by β2-adrenergic receptors and cAMP is PKA independent: evidence for EPAC involvement. Am J Physiol Lung Cell Mol Physiol 2008, 294:L131-L138.
• [49]Roscioni SS, Kistemaker LE, Menzen MH, Elzinga CR, Gosens R, Halayko AJ, Meurs H, Schmidt M: PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells. Respir Res 2009, 10:88. BioMed Central Full Text
• [50]Barnes P: Biochemical basis of asthma therapy. J Biol Chem 2011, 38:32899-32905.
• [51]Moir LM, Trian T, Ge Q, Berger P, Burgess JK, Oliver BG, Black JL: Phosphatidylinositol 3-kinase isoform-specific effects in airway mesenchymal cell function. J Pharmacol Exp Ther 2011, 337:557-566.
• [52]Ge Q, Moir LM, Trian T, Niimi K, Poniris M, Shepherd PR, Black JL, Oliver BG, Burgess JK: The phosphoinositide 3’-kinase p110δ modulates contractile protein production and IL-6 release in human airway smooth muscle. J Cell Physiol 2012, 22:3044-3052.
• [53]Spears M, Donnelly I, Jolly L, Brannigan M, Ito K, McSherry C, Lafferty J, Chauduri R, Braganza G, Bareille P, Sweeney L, Adcock IM, Barnes PJ, Wood S, Thomson NC: Bronchodilatory effect of the PPAR-gamma agonist rosiglitazone in smokers with asthma. Clin Pharmacol Ther 2009, 86:49-53.
• [54]Wan Y, Evans RM: Rosiglitazone activation of PPARgamma suppresses fractalkine signalling. J Mol Endocrinol 2010, 44:135-142.
• [55]Nicola T, Ambalavanan N, Zhang W, James ML, Rehan V, Halloran B, Olave N, Bulger A, Oparil S, Chen YF: Hypoxia-induced inhibition of lung development is attenuated by the peroxisome proliferator-activated receptor-γ agonist rosiglitazone. Am J Physiol Lung Cell Mol Physiol 2011, 301:L125-L134.
• [56]Guo N, Woeller CF, Feldon SE, Phipps RP: Peroxisome proliferator-activated receptor gamma ligands inhibit transforming growth factor-beta-induced, hyaluronan-dependent, T cell adhesion to orbital fibroblasts. J Biol Chem 2011, 286:188856-188867.
• [57]Marx N, Mach F, Sauty A, Leung JH, Sarafi MN, Ransohoff RM, Libby P, Plutzky J, Luster AD: Peroxisome proliferator-activated receptor-γ activators inhibit IFN-γ-induced expression of the T cell-active CXC chemokines IP-10, Mig, and ITAC in human endothelial cells. J Immunol 2000, 164:6503-6508.
• [58]Natarajan C, Bright JJ: Peroxisome proliferator-activated receptor-gamma agonists inhibit experimental allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1 differentiation. Genes Immun 2002, 3:59-70.