Am. J. Respir. Crit. Care Med., Volume 165, Number 8, April 2002, 1161-1171

Selective Induction of Eotaxin Release by Interleukin-13 or Interleukin-4 in Human Airway Smooth Muscle Cells Is Synergistic with Interleukin-1 and Is Mediated by the Interleukin-4 Receptor -Chain

Stuart J. Hirst, Matthew P. Hallsworth, Qi Peng, and Tak H. Lee

Department of Respiratory Medicine and Allergy, The Guy's, King's and St. Thomas' School of Medicine, King's College London, Guy's Hospital Campus, London, United Kingdom

The biologic activities of interleukin (IL)-13 and IL-4 often overlap, and evidence supports their importance in atopic disease and airways hyperresponsiveness. Here, their capacity to release eosinophil-activating cytokines was examined in cultured human airway smooth muscle. IL-13 and IL-4 induced selective release of eotaxin with no effect on granulocyte-macrophage colony-stimulating factor, regulated upon activation, normal T-cell expressed and secreted (RANTES), or IL-8. A profound synergistic increase in eotaxin release occurred when IL-13 or IL-4 was combined with IL-1 that was abrogated by a neutralizing antibody to the IL-4 receptor  (IL-4R)-chain but not to the IL-2 receptor  (IL-2R)-chain. Expression of cell surface IL-4 receptors and IL-4R in lysates was constitutive and unchanged by treatment with IL-13 or IL-4 alone or in combination with IL-1. Activation of IL-4R by IL-13 or IL-4 induced signal transducer and activation of transcription-6 (STAT6), p42/ p44 ERK, p38, and to a lesser extent, SAPK/JNK mitogen-activated protein kinase phosphorylation. STAT6 and MAP kinase activation by IL-13 or IL-4 was not further potentiated after combined stimulation with IL-1. However, eotaxin release induced by IL-13 or IL-4 alone, and in combination with IL-1, was prevented by the MEK inhibitor U 0126 and by the p38 inhibitor SB 202190. Collectively, the data suggest that selective eotaxin release induced either by IL-13 and IL-4 or when combined with IL-1 is mediated by a constitutive cell surface IL-4R and the activation of multiple intracellular pathways.

This article has been cited by other articles:

				Q. Wu, R. J. Martin, S. LaFasto, B. J. Efaw, J. G. Rino, R. J. Harbeck, and H. W. Chu Toll-like Receptor 2 Down-regulation in Established Mouse Allergic Lungs Contributes to Decreased Mycoplasma Clearance Am. J. Respir. Crit. Care Med., April 1, 2008; 177(7): 720 - 729. [Abstract] [Full Text] [PDF]

				S. Siddiqui, F. Hollins, S. Saha, and C. E. Brightling Inflammatory cell microlocalisation and airway dysfunction: cause and effect? Eur. Respir. J., December 1, 2007; 30(6): 1043 - 1056. [Abstract] [Full Text] [PDF]

				K. Parameswaran, K. Radford, A. Fanat, J. Stephen, C. Bonnans, B. D. Levy, L. J. Janssen, and P. G. Cox Modulation of Human Airway Smooth Muscle Migration by Lipid Mediators and Th-2 Cytokines Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 240 - 247. [Abstract] [Full Text] [PDF]

				A. J. Ammit, L. M. Moir, B. G. Oliver, J. M. Hughes, H. Alkhouri, Q. Ge, J. K. Burgess, J. L. Black, and M. Roth Effect of IL-6 trans-signaling on the pro-remodeling phenotype of airway smooth muscle Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L199 - L206. [Abstract] [Full Text] [PDF]

				M. S. Rahman, A. Yamasaki, J. Yang, L. Shan, A. J. Halayko, and A. S. Gounni IL-17A Induces Eotaxin-1/CC Chemokine Ligand 11 Expression in Human Airway Smooth Muscle Cells: Role of MAPK (Erk1/2, JNK, and p38) Pathways J. Immunol., September 15, 2006; 177(6): 4064 - 4071. [Abstract] [Full Text] [PDF]

				B. L. Bennett c-Jun N-terminal kinase-dependent mechanisms in respiratory disease. Eur. Respir. J., September 1, 2006; 28(3): 651 - 661. [Abstract] [Full Text] [PDF]

				A. S. Gounni The high-affinity IgE receptor (Fc{epsilon}RI): a critical regulator of airway smooth muscle cells? Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L312 - L321. [Abstract] [Full Text] [PDF]

				V. Chan, J. K. Burgess, J. C. Ratoff, B. J. O'Connor, A. Greenough, T. H. Lee, and S. J. Hirst Extracellular Matrix Regulates Enhanced Eotaxin Expression in Asthmatic Airway Smooth Muscle Cells Am. J. Respir. Crit. Care Med., August 15, 2006; 174(4): 379 - 385. [Abstract] [Full Text] [PDF]

				A Sutcliffe, D Kaur, S Page, L Woodman, C L Armour, M Baraket, P Bradding, J M Hughes, and C E Brightling Mast cell migration to Th2 stimulated airway smooth muscle from asthmatics Thorax, August 1, 2006; 61(8): 657 - 662. [Abstract] [Full Text] [PDF]

				R. Issa, S. Xie, K.-Y. Lee, R. D. Stanbridge, P. Bhavsar, M. B. Sukkar, and K. F. Chung GRO-{alpha} regulation in airway smooth muscle by IL-1beta and TNF-{alpha}: role of NF-{kappa}B and MAP kinases Am J Physiol Lung Cell Mol Physiol, July 1, 2006; 291(1): L66 - L74. [Abstract] [Full Text] [PDF]

				T. Morokata, K. Suzuki, Y. Masunaga, K. Taguchi, K. Morihira, I. Sato, M. Fujii, S. Takizawa, Y. Torii, N. Yamamoto, et al. A Novel, Selective, and Orally Available Antagonist for CC Chemokine Receptor 3 J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 244 - 250. [Abstract] [Full Text] [PDF]

				D. S. Faffe, L. Flynt, K. Bourgeois, R. A. Panettieri Jr., and S. A. Shore Interleukin-13 and Interleukin-4 Induce Vascular Endothelial Growth Factor Release from Airway Smooth Muscle Cells: Role of Vascular Endothelial Growth Factor Genotype Am. J. Respir. Cell Mol. Biol., February 1, 2006; 34(2): 213 - 218. [Abstract] [Full Text] [PDF]

				A. S. Gounni, V. Wellemans, J. Yang, F. Bellesort, K. Kassiri, S. Gangloff, M. Guenounou, A. J. Halayko, Q. Hamid, and B. Lamkhioued Human Airway Smooth Muscle Cells Express the High Affinity Receptor for IgE (Fc{epsilon}RI): A Critical Role of Fc{epsilon}RI in Human Airway Smooth Muscle Cell Function J. Immunol., August 15, 2005; 175(4): 2613 - 2621. [Abstract] [Full Text] [PDF]

				P. Joubert, S. Lajoie-Kadoch, I. Labonte, A. S. Gounni, K. Maghni, V. Wellemans, J. Chakir, M. Laviolette, Q. Hamid, and B. Lamkhioued CCR3 Expression and Function in Asthmatic Airway Smooth Muscle Cells J. Immunol., August 15, 2005; 175(4): 2702 - 2708. [Abstract] [Full Text] [PDF]

				G. E. Morris, M. K. B. Whyte, G. F. Martin, P. J. Jose, S. K. Dower, and I. Sabroe Agonists of Toll-like Receptors 2 and 4 Activate Airway Smooth Muscle via Mononuclear Leukocytes Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 814 - 822. [Abstract] [Full Text] [PDF]

				W. Duan, J. H. P. Chan, K. McKay, J. R. Crosby, H. H. Choo, B. P. Leung, J. G. Karras, and W. S. F. Wong Inhaled p38{alpha} Mitogen-activated Protein Kinase Antisense Oligonucleotide Attenuates Asthma in Mice Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 571 - 578. [Abstract] [Full Text] [PDF]

				S.-Y. Eum, K. Maghni, B. Tolloczko, D. H. Eidelman, and J. G. Martin IL-13 may mediate allergen-induced hyperresponsiveness independently of IL-5 or eotaxin by effects on airway smooth muscle Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L576 - L584. [Abstract] [Full Text] [PDF]

				A. Hoshino, T. Tsuji, J. Matsuzaki, T. Jinushi, S. Ashino, T. Teramura, K. Chamoto, Y. Tanaka, Y. Asakura, T. Sakurai, et al. STAT6-mediated signaling in Th2-dependent allergic asthma: critical role for the development of eosinophilia, airway hyper-responsiveness and mucus hypersecretion, distinct from its role in Th2 differentiation Int. Immunol., October 1, 2004; 16(10): 1497 - 1505. [Abstract] [Full Text] [PDF]

				C E Brightling and I D Pavord Location, location, location: microlocalisation of inflammatory cells and airway dysfunction Thorax, September 1, 2004; 59(9): 734 - 735. [Full Text] [PDF]

				A. S. Gounni, Q. Hamid, S. M. Rahman, J. Hoeck, J. Yang, and L. Shan IL-9-Mediated Induction of Eotaxin1/CCL11 in Human Airway Smooth Muscle Cells J. Immunol., August 15, 2004; 173(4): 2771 - 2779. [Abstract] [Full Text] [PDF]

				T. Kikuchi, J. D. Shively, J. S. Foley, J. M. Drazen, and D. J. Tschumperlin Differentiation-dependent responsiveness of bronchial epithelial cells to IL-4/13 stimulation Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L119 - L126. [Abstract] [Full Text] [PDF]

				W. Duan, J. H. P. Chan, C. H. Wong, B. P. Leung, and W. S. F. Wong Anti-Inflammatory Effects of Mitogen-Activated Protein Kinase Kinase Inhibitor U0126 in an Asthma Mouse Model J. Immunol., June 1, 2004; 172(11): 7053 - 7059. [Abstract] [Full Text] [PDF]

				G. Dent, C. Hadjicharalambous, T. Yoshikawa, R. L. C. Handy, J. Powell, I. K. Anderson, R. Louis, D. E. Davies, and R. Djukanovic Contribution of Eotaxin-1 to Eosinophil Chemotactic Activity of Moderate and Severe Asthmatic Sputum Am. J. Respir. Crit. Care Med., May 15, 2004; 169(10): 1110 - 1117. [Abstract] [Full Text] [PDF]

				M. A. Aronica, S. McCarthy, S. Swaidani, D. Mitchell, M. Goral, J. R. Sheller, and M. Boothby Recall Helper T Cell Response: T Helper 1 Cell-resistant Allergic Susceptibility without Biasing Uncommitted CD4 T Cells Am. J. Respir. Crit. Care Med., March 1, 2004; 169(5): 587 - 595. [Abstract] [Full Text] [PDF]

				S. J. McMillan, J. Kearley, J. D. Campbell, X.-W. Zhu, K. Y. Larbi, J. M. Shipley, R. M. Senior, S. Nourshargh, and C. M. Lloyd Matrix Metalloproteinase-9 Deficiency Results in Enhanced Allergen-Induced Airway Inflammation J. Immunol., February 15, 2004; 172(4): 2586 - 2594. [Abstract] [Full Text] [PDF]

				M. W. Wynes and D. W. H. Riches Induction of Macrophage Insulin-Like Growth Factor-I Expression by the Th2 Cytokines IL-4 and IL-13 J. Immunol., October 1, 2003; 171(7): 3550 - 3559. [Abstract] [Full Text] [PDF]

				D. S. Faffe, T. Whitehead, P. E. Moore, S. Baraldo, L. Flynt, K. Bourgeois, R. A. Panettieri, and S. A. Shore IL-13 and IL-4 promote TARC release in human airway smooth muscle cells: role of IL-4 receptor genotype Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L907 - L914. [Abstract] [Full Text] [PDF]

				H. C. Atherton, G. Jones, and H. Danahay IL-13-induced changes in the goblet cell density of human bronchial epithelial cell cultures: MAP kinase and phosphatidylinositol 3-kinase regulation Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L730 - L739. [Abstract] [Full Text] [PDF]

				J. Reibman, Y. Hsu, L. C. Chen, B. Bleck, and T. Gordon Airway Epithelial Cells Release MIP-3{alpha}/CCL20 in Response to Cytokines and Ambient Particulate Matter Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 648 - 654. [Abstract] [Full Text] [PDF]

				S. Baraldo, D. S. Faffe, P. E. Moore, T. Whitehead, M. McKenna, E. S. Silverman, R. A. Panettieri Jr., and S. A. Shore Interleukin-9 influences chemokine release in airway smooth muscle: role of ERK Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L1093 - L1102. [Abstract] [Full Text] [PDF]

				M. J. Tobin Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2002 Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 319 - 332. [Full Text] [PDF]

				S. E. Wenzel, J. B. Trudeau, S. Barnes, X. Zhou, M. Cundall, J. Y. Westcott, K. McCord, and H. W. Chu TGF-{beta} and IL-13 Synergistically Increase Eotaxin-1 Production in Human Airway Fibroblasts J. Immunol., October 15, 2002; 169(8): 4613 - 4619. [Abstract] [Full Text] [PDF]