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IL-4 and IL-13 Stimulate Human Bronchial Epithelial Cells to Release IL-8

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Abstract

Cytokine networks are important in regulating the traffic of inflammatory cells in the airways. Interleukin-8 (IL-8) released by human bronchial epithelial cells (HBECs) is thought to be of particular importance in attracting neutrophils and monocytes to sites of inflammation. Increased release of IL-8 by HBECs in response to Th-1 cytokines such as TNF alpha and IL-1 beta may be an important pathophysiologic pathway. The present study was designed to explore the role of the Th2 cytokine IL-4 and the functionally related interleukins IL-10, and IL-13 on the regulation of IL-8 release by HBECs. HBECs (passage 4–6) were cultured in LHC9/RPMI and when confluent cells were stimulated in unsupplemented medium LHCD/RPMI by IL-4, IL-10, and IL-13 at 10 ng/ml concentration for all cytokines. TNF alpha stimulation was used as a positive control. After 24 hours supernatants were collected and tested for IL-8 by a sandwich ELISA. Unstimulated HBECs spontaneously released limited amounts of IL-8 (11 ± 1 pM) and significantly increased cytokine production in response to IL-4 (42 ± 1 pM), IL-13 (30 ± 1 pM) and TNF (128 ± 11 pM). Stimulation with IL-10 (11 ± 1 pM) did not change basal production of IL-8. When HBECs were co-stimulated with IL-4 plus TNF, the production of IL-8 was further increased (204 ± 5 pM). In contrast, IL-10 attenuated the effect of TNF during co-stimulation (82 ± 5 pM). IL-13 did not affect the release of IL-8 induced by TNF (111 ± 9 pM). Northern blot analysis of IL-8 mRNA levels showed the highest induction of IL-8 mRNA in HBECs co-stimulated with TNF and IL-4. We conclude from our study that IL-4 directly induces IL-8 release from HBECs and amplifies the release of IL-8 in response to TNF alpha. IL-13 is less active and IL-10 has an inhibitory effect. Airway epithelial cells are able to interact, therefore, with products of both Th1 and Th2 cells with respect to modulating release of IL-8.

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REFERENCES

  1. Raeburn, D. and S. E. Webber. 1994. Proinflammatory potential of the airway epithelium in bronchial asthma. Eur. Respir. J. 7:2226-2233.

    Google Scholar 

  2. Rennard, S. I., D. J. Romberger, J. H. Sissons, S. G. von Essen, I. Rubinstein, R. A. Robbins, and J. R. Spurzem. 1994. Airway epithelial cells: functional roles in airway disease. Am. J. Respir. Crit. Care Med. 150:527-530.

    Google Scholar 

  3. Strieter, R. M., N. W. Lukacs, T. J. Standiford, and S. L. Kunkel. 1993. Cytokines and lung inflammation: mechanisms of neutrophil recruitment to the lung. Thorax 48:765-769.

    Google Scholar 

  4. Baggiolini, M., P. Imboden, and P. Detmers. 1992. Neutrophil activation and the effects of interleukin-8/neutrophil-activating peptide 1 (IL-8/NAP-1). In: Baggiolini, M., Sorg, C., eds. Interleukin-8 (NAP-1) and related chemotactic cytokines. Basel (Switzerland): Karger, pp. 1-17.

    Google Scholar 

  5. Detmers, P. A., S. K. Lo, E. Olsen-Egbert, A. Walz, M. Baggiolini, and Z. A. Cohn. 1990. Neutrophil-activating protein 1/interleukin-8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils. J. Exp. Med. 171:1155-1162.

    Google Scholar 

  6. Wymann, M. P., P. Kernen, D. A. Deranleau, B. Dewald, V. von Tscharner, and M. Baggiolini. 1987. Oscillatory motion in human neutrophils responding to chemotactic stimuli. Biochem. Biophys. Res. Commun. 147:361-368.

    Google Scholar 

  7. Leonard, E. J., T. Yoshimura, S. Tanaka, and M. Raffeld. 1991. Neutrophil recruitment by intradermally injected neutrophil attractant/activating protein-1 (NAP-1) in human subjects. J. Invest. Dermatol. 96:690-694.

    Google Scholar 

  8. Miller, E. J., A. B. Cohen, S. Nagao, D. Griffith, R. J. Maunder, T. R. Martin, J. P. Weiner-Kronish, M. Sticherling, E. Christophers, and M. A. Matthay. 1992. Elevated levels of NAP-1/Interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am. Rev. Respir. Dis. 146:427-432.

    Google Scholar 

  9. Car, B. D., F. Meloni, M. Luisetti, G. Semenzato, G. Gialdroni-Grassi, and A. Walz. 1994. Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am. J. Respir. Crit. Care Med. 149:655-659.

    Google Scholar 

  10. Konno, S., Y. Gonokami, M. Kurokawa, K. Kawazu, K. Asano, K. Okamoto, and M. Adachi. 1996. Cytokine concentrations in sputum of asthmatic patients. Int. Arch. Allergy Immunol. 109:73-78.

    Google Scholar 

  11. Levine, S. J., P. Larivee, C. Logun, C. W. Angus, and J. H. Shelhamer. 1993. Corticosteroids differentially regulate secretion of IL-6, IL-8, and G-CSF by a human bronchial epithelial cell line. Am. J. Physiol. 265:L360-L368.

    Google Scholar 

  12. Vittori, E., F. Sciacca, F. Colotta, A. Mantovani, and S. Mattoli. 1992. Protective effect of nedocromil sodium on the interleukin-1 induced production of interleukin-8 in human bronchial epithelial cells. J. Allergy Clin. Immunol. 90:76-84.

    Google Scholar 

  13. Romagnani, S. 1995. Biology of human Th1 and Th2 cells. J. Clin. Immunol. 15:121-129.

    Google Scholar 

  14. Maestrelli, P., A. Di Stefano, P. Occari, G. Turato, G. Milani, F. Pivirotto, C. E. Mapp, L. M. Fabbri, and M. Saetta. 1995. Cytokines in the airway mucosa of subjects with asthma induced by toluene diisocyanate. Am. J. Respir. Crit. Care Med. 151:607-612.

    Google Scholar 

  15. Umetsu, D. T. and R. H. De Kruyff. 1997. Th1 and Th2 CD4+ cells in human allergic diseases. J. Allergy Clin. Immunol. 100:1-6.

    Google Scholar 

  16. Swain, S. L. 1994. IL-4 dictates T-cell differentiation. Res. Immunol. 144:616-620.

    Google Scholar 

  17. O'Garra, A., S. E. Macatonia, C. S. Hsieh, and K. M. Murphy. 1994. Regulatory role of IL-4 and other cytokines in T helper cell development in an abTCR transgenic mouse system. Res. Immunol. 144:620-625.

    Google Scholar 

  18. Paul, W. E. 1992. The role of IL-4 in the regulation of B cell development, growth, and differentiation. In: Spits, H., ed. IL-4: Structure and Function. CRC Press, Boca Raton, Florida: pp. 58-73.

    Google Scholar 

  19. De Waal Melafyt, R., H. Yssel, M.-G. Roncarolo, H. Spits, and J. E. De Vries. 1992. Interleukin-10. Curr. Opinion. Immun. 314-320.

  20. Moore, K. W., A. O'Garra, R. De Waal Malefyt, P. Vierra, and T. R. Mosmann, 1993. Interleukin-10. Ann. Rev. Immunol. 11:165-190.

    Google Scholar 

  21. Pretolani, M. and M. Goldman. 1997. IL-10: a potential therapy for allergic inflammation. Immunol. Today 18:277-280.

    Google Scholar 

  22. Fiorentino, D. F., A. Zlotnik, T. R. Mosmann, M. Howard, and A. O'Gara. 1991. IL-10 inhibits cytokine production by activated macrophages. J. Immunol. 147:3815-3822.

    Google Scholar 

  23. Casatella, M. A., L. Meda, S. Bonora, M. Ceska, and G. Constantini. 1993. Interleukin-10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. J. Exp. Med. 178:2207-2211.

    Google Scholar 

  24. Mosmann, T. R. 1994. Interleukin-10. In: Thompson, A. W., ed. The Cytokine Handbook. Academic Press, San Diego, California: pp. 223-237.

    Google Scholar 

  25. Zurawski, G. and J. E. De Vries. 1994. Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. Immunol. Today 15:19-26.

    Google Scholar 

  26. Zurawski, S. M., F. Vega Jr., B. Huyghe, and G. Zurawski. 1993. Receptors for interleukin-13 and interleukin-4 are complex and share a novel component that functions in signal transduction. EMBO J. 12:2663-2670.

    Google Scholar 

  27. Kelsen, S. G., I. A. Mardini, S. Zhou, J. L. Benovic, and N. C. Higgins. 1992. A technique to harvest viable tracheobronchial epithelial cells from living human donors. Am. J. Respir. Cell Mol. Biol. 7:66-72.

    Google Scholar 

  28. Beckman, J. D., H. Takizawa, D. Romberger, M. Illig, L. Classen, K. Rickard, and S. I. Rennard. 1992. Serum-free culture of fractionated bovine bronchial epithelial cells. In: Vitro Cell. Dev. Biol. 28A:39-46.

    Google Scholar 

  29. Boyce, S. T., and R. G. Ham. 1985. Cultivation, frozen storage, and clonal growth of normal epidermal keratinocytes in serum free media. J. Tissue Cult. Methods 9:83-93.

    Google Scholar 

  30. Chomczynski, P. and N. Sacchi. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analyt. Biochem. 162:156-159.

    Google Scholar 

  31. Kwon, O. J., T. Bo, P. D. Collins, I. M. Adcock, J. C. Mak, R. R. Robbins, K. F. Chung, and P. J. Barnes. 1994. Tumor necrosis factor-induced interleukin-8 expression in cultured human airway epithelial cells. Am. J. Physiol. 267:L398-L405.

    Google Scholar 

  32. Robbins, R. A., P. J. Barnes, D. R. Springall, J. B. Warren, O. J. Kwon, L. D. K. Buttery, A. J. Wilson, D. A. Geller, and J. M. Polak. 1994. Expression of inducible nitric oxide synthase in human lung epithelial cells. Biochem. Biophys. Res. Commun. 203:209-218.

    Google Scholar 

  33. Colgan, S. P., M. B. Resnick, C. A. Parkos, C. Delp-Archer, D. McGuirk, A. E. Bacarra, P. F. Weller, and J. L. Madara. 1994. IL-4 directly modulates function of a model human intestinal epithelium. J. Immunol. 153:2122-2129.

    Google Scholar 

  34. Postlethwaite, A. E. and J. M. Seyer. 1991. Fibroblast chemotaxis induction by a recombinant IL-4. J. Clin. Invest. 87:1240.

    Google Scholar 

  35. Piela-Smith, T. H., G. Broketa, A. Hand, and J. H. Korn. 1992. Regulation of ICAM-1 expression and function in human dermal fibroblasts by IL-4. J. Immunol. 148:1375-1381.

    Google Scholar 

  36. Leung, K. N., N. K. Mak, M. C. Fung, and A. J. Hapel. 1994. Synergistic effect of IL-4 and TNF-alpha in the induction of monocytic differentiation of a mouse myeloid leukaemic cell line (WEHI-3B JCS). Immunology 81:65-72.

    Google Scholar 

  37. Cromwell, O., Q. Hamid, C. J. Corrigan, J. Barkans, Q. Meng, P. D. Collins, and A. B. Kay. 1992. Expression and generation of interleukin-8, IL-6 and granulocyte-macrophage colony-stimulating factor by bronchial epithelial cells and enhancement by IL-1 beta and tumor necrosis factor-alpha. Immunology 77:330-337.

    Google Scholar 

  38. Erger, R. A., and T. B. Casale. 1995. Interleukin-8 is a potent mediator of eosinophil chemotaxis through endothelium and epithelium. Am. J. Physiol. 268:L117-L122.

    Google Scholar 

  39. Mio, T., D. J. Romberger, A. B. Thompson, R. A. Robbins, A. Heires, and S. I. Rennard. 1997. Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells. Am. J. Respir. Crit. Care Med. 155:1770-1776.

    Google Scholar 

  40. Adachi, Y., T. Mio, K. Takigawa, I. Striz, D. J. Romberger, R. A. Robbins, J. R. Spurzem, P. Heires, and S. I. Rennard. 1997. Mutual inhibition by TGF-b and IL-4 in cultured human bronchial epithelial cells. Am. J. Physiol. 273:L701-L708.

    Google Scholar 

  41. Marone, G. 1998. Asthma: recent advances. Immunol. Today 19:5-9.

    Google Scholar 

  42. Massion, P. P., H. Inoue, J. Richman-Eisenstat, D. Gruneberger, P. G. Jorens, B. Housset, J. F. Pittet, J. P. Wiener-Kronish, and J. A. Nadel. 1994. Novel Pseudomonas product stimulates interleukin-8 production in airway epithelial cells in vitro. J. Clin. Invest. 93:26-32.

    Google Scholar 

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Authors and Affiliations

  1. Department of Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

    I. Stříž

  2. Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska

    T. Mio, Y. Adachi & S. I. Rennard

  3. Veterans Administration Hospital, Omaha, Nebraska

    R. A. Robbins & D. J. Romberger

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Stříž, I., Mio, T., Adachi, Y. et al. IL-4 and IL-13 Stimulate Human Bronchial Epithelial Cells to Release IL-8. Inflammation 23, 545–555 (1999). https://doi.org/10.1023/A:1020242523697

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