IL-13 and IL-4 promote TARC release in human airway smooth muscle cells: role of IL-4 receptor genotype.

The chemokine thymus- and activation-regulated chemokine (TARC) induces selective migration of Th2, but not Th1, lymphocytes and is upregulated in the airways of asthmatic patients. The purpose of this study was to determine whether human airway smooth muscle (HASM) cells produce TARC. Neither IL-4, IL-13, IL-1beta, IFN-gamma, nor TNF-alpha alone stimulated TARC release into the supernatant of cultured HASM cells. However, both IL-4 and IL-13 increased TARC protein and mRNA expression when administered in combination with TNF-alpha but not IL-1beta or IFN-gamma. Macrophage-derived chemokine was not expressed under any of these conditions. TARC release induced by TNF-alpha + IL-13 or TNF-alpha + IL-4 was inhibited by the beta-agonist isoproterenol and by other agents that activate protein kinase A, but not by dexamethasone. To determine whether polymorphisms of the IL-4Ralpha have an impact on the ability of IL-13 or IL-4 to induce TARC release, HASM cells from multiple donors were genotyped for the Ile50Val, Ser478Pro, and Gln551Arg polymorphisms of the IL-4Ralpha. Our data indicate that cells expressing the Val50/Pro478/Arg551 haplotype had significantly greater IL-13- or IL-4-induced TARC release than cells with other IL-4Ralpha genotypes. These data indicate that Th2 cytokines enhance TARC expression in HASM cells in an IL-4Ralpha genotype-dependent fashion and suggest that airway smooth muscle cells participate in a positive feedback loop that promotes the recruitment of Th2 cells into asthmatic airways.

[1]  K. Fukuda,et al.  Differential expression of thymus- and activation-regulated chemokine (CCL17) and macrophage-derived chemokine (CCL22) by human fibroblasts from cornea, skin, and lung. , 2003, The Journal of allergy and clinical immunology.

[2]  Jonathan A. Bernstein,et al.  V75R576 IL-4 Receptor α Is Associated with Allergic Asthma and Enhanced IL-4 Receptor Function1 , 2002, The Journal of Immunology.

[3]  Tak H. Lee,et al.  Selective induction of eotaxin release by interleukin-13 or interleukin-4 in human airway smooth muscle cells is synergistic with interleukin-1beta and is mediated by the interleukin-4 receptor alpha-chain. , 2002, American journal of respiratory and critical care medicine.

[4]  R. Panettieri,et al.  IL-13 and IL-4 cause eotaxin release in human airway smooth muscle cells: a role for ERK. , 2002, American journal of physiology. Lung cellular and molecular physiology.

[5]  G. O'Neill,et al.  Tumor Necrosis Factor- α –Induced Secretion of RANTES and Interleukin-6 from Human Airway Smooth Muscle Cells: Modulation by Glucocorticoids and β -Agonists , 2002 .

[6]  N. Bottini,et al.  IL‐4 receptor alpha chain genetic polymorphism and total IgE levels in the English population: two‐locus haplotypes are more informative than individual SNPs , 2002, Clinical genetics.

[7]  B. Ma,et al.  IL-13-Induced Chemokine Responses in the Lung: Role of CCR2 in the Pathogenesis of IL-13-Induced Inflammation and Remodeling1 , 2002, The Journal of Immunology.

[8]  K. Matsushima,et al.  Increased levels of a TH2‐type CC chemokine thymus and activation‐regulated chemokine (TARC) in serum and induced sputum of asthmatics , 2002, Allergy.

[9]  D. Postma,et al.  Gene-gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma. , 2002, American journal of human genetics.

[10]  R. Chakraborty,et al.  V75R576 IL-4 receptor alpha is associated with allergic asthma and enhanced IL-4 receptor function. , 2002, Journal of immunology.

[11]  A. Konno,et al.  Expression of C–C chemokine TARC in human nasal mucosa and its regulation by cytokines , 2001, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[12]  R. Panettieri,et al.  Selected Contribution: Synergism between TNF-α and IL-1β in airway smooth muscle cells: implications for β-adrenergic responsiveness , 2001 .

[13]  J. Kinet,et al.  Direct effects of interleukin-13 on signaling pathways for physiological responses in cultured human airway smooth muscle cells. , 2001, American journal of respiratory and critical care medicine.

[14]  R. Panettieri,et al.  Interleukin-6 family cytokines: signaling and effects in human airway smooth muscle cells. , 2001, American journal of physiology. Lung cellular and molecular physiology.

[15]  L. Fabbri,et al.  The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics. , 2001, The Journal of clinical investigation.

[16]  K. Deichmann,et al.  A novel polymorphism in the 5′ promoter region of the human interleukin-4 receptor α-chain gene is associated with decreased soluble interleukin-4 receptor protein levels , 2001, Immunogenetics.

[17]  M. Kagnoff,et al.  Regulated production of the T helper 2-type T-cell chemoattractant TARC by human bronchial epithelial cells in vitro and in human lung xenografts. , 2001, American journal of respiratory cell and molecular biology.

[18]  I. Homma,et al.  Intervention of Thymus and Activation-Regulated Chemokine Attenuates the Development of Allergic Airway Inflammation and Hyperresponsiveness in Mice1 , 2001, The Journal of Immunology.

[19]  A. Knox,et al.  Regulation of TNF‐α‐induced eotaxin release from cultured human airway smooth muscle cells by β2‐agonists and corticosteroids , 2001 .

[20]  M. Yacoub,et al.  Effects of Prostaglandin E2 and cAMP Elevating Drugs on GM-CSF Release by Cultured Human Airway Smooth Muscle Cells , 2001 .

[21]  V. Casolaro,et al.  Interleukin-13 upregulates eotaxin expression in airway epithelial cells by a STAT6-dependent mechanism. , 2001, American journal of respiratory cell and molecular biology.

[22]  M. Yacoub,et al.  Effects of prostaglandin E2 and cAMP elevating drugs on GM-CSF release by cultured human airway smooth muscle cells. Relevance to asthma therapy. , 2001, American journal of respiratory cell and molecular biology.

[23]  A. Knox,et al.  Regulation of TNF-alpha-induced eotaxin release from cultured human airway smooth muscle cells by beta2-agonists and corticosteroids. , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[24]  K. Fukuda,et al.  Synergistic effect of TNF-alpha and IL-4 on the expression of thymus- and activation-regulated chemokine in human corneal fibroblasts. , 2000, Biochemical and biophysical research communications.

[25]  A. Ammit,et al.  Tumor necrosis factor-alpha-induced secretion of RANTES and interleukin-6 from human airway smooth-muscle cells. Modulation by cyclic adenosine monophosphate. , 2000, American journal of respiratory cell and molecular biology.

[26]  R. Pawankar,et al.  Inducible Expression of a Th2-Type CC Chemokine Thymus- and Activation-Regulated Chemokine by Human Bronchial Epithelial Cells1 , 2000, The Journal of Immunology.

[27]  I. Hall.  Interleukin-4 receptor alpha gene variants and allergic disease , 2000, Respiratory research.

[28]  A. Tsalenko,et al.  Variation in the interleukin 4-receptor alpha gene confers susceptibility to asthma and atopy in ethnically diverse populations. , 2000, American journal of human genetics.

[29]  I. Adcock,et al.  Molecular mechanisms of corticosteroid actions. , 2000, Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace.

[30]  V. Casolaro,et al.  Activation of Eotaxin Gene Transcription by NF-κB and STAT6 in Human Airway Epithelial Cells , 1999, The Journal of Immunology.

[31]  J. Heyder,et al.  Glucocorticoids ablate IL-1β-induced β-adrenergic hyporesponsiveness in human airway smooth muscle cells. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[32]  R. Panettieri,et al.  Dexamethasone Pathway That Is Only Partially Sensitive to B-dependent Signaling Κ Involves an Nf- Human Tracheal Smooth Muscle Cells Up-regulation of Icam-1 by Cytokines In , 2013 .

[33]  T. Arinami,et al.  No association between atopy/asthma and the ILe50Val polymorphism of IL-4 receptor. , 1999, American journal of respiratory and critical care medicine.

[34]  J. Ryan,et al.  Cutting edge: effects of an allergy-associated mutation in the human IL-4R alpha (Q576R) on human IL-4-induced signal transduction. , 1999, Journal of immunology.

[35]  Sparholt,et al.  The polymorphisms S503P and Q576R in the interleukin‐4 receptor α gene are associated with atopy and influence the signal transduction , 1999, Immunology.

[36]  K. Ihara,et al.  Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis. , 1999, Journal of immunology.

[37]  Shibasaki,et al.  Lack of association of atopy/asthma and the interleukin‐4 receptor α gene in Japanese , 1999, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[38]  K. Matsushima,et al.  Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. , 1999, International immunology.

[39]  V. Casolaro,et al.  Activation of eotaxin gene transcription by NF-kappa B and STAT6 in human airway epithelial cells. , 1999, Journal of immunology.

[40]  W. Paul,et al.  The IL-4 receptor: signaling mechanisms and biologic functions. , 1999, Annual review of immunology.

[41]  A. Knox,et al.  Role of cyclo‐oxygenase‐2 induction in interleukin‐1β induced attenuation of cultured human airway smooth muscle cell cyclic AMP generation in response to isoprenaline , 1998, British journal of pharmacology.

[42]  J. Heyder,et al.  Prostanoids mediate IL-1β-induced β-adrenergic hyporesponsiveness in human airway smooth muscle cells. , 1998, American journal of physiology. Lung cellular and molecular physiology.

[43]  J. Zamorano,et al.  A Role for the Insulin-Interleukin (IL)-4 Receptor Motif of the IL-4 Receptor α-Chain in Regulating Activation of the Insulin Receptor Substrate 2 and Signal Transducer and Activator of Transcription 6 Pathways , 1998, The Journal of Biological Chemistry.

[44]  R. Puri,et al.  Structure of and signal transduction through interleukin-4 and interleukin-13 receptors (review). , 1998, International journal of molecular medicine.

[45]  N. Hamasaki,et al.  Ile50Val variant of IL4R alpha upregulates IgE synthesis and associates with atopic asthma. , 1998, Nature genetics.

[46]  T. Chatila,et al.  The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. , 1997, The New England journal of medicine.

[47]  I. Hall,et al.  Effect of IL-1 beta on responses of cultured human airway smooth muscle cells to bronchodilator agonists. , 1997, American journal of respiratory cell and molecular biology.

[48]  K. Chung,et al.  Human airway smooth muscle cells express and release RANTES in response to T helper 1 cytokines: regulation by T helper 2 cytokines and corticosteroids. , 1997, Journal of immunology.

[49]  R. Panettieri,et al.  A human airway smooth muscle cell line that retains physiological responsiveness. , 1989, The American journal of physiology.