Journal Mobile Options
Table of Contents
Vol. 117, No. 1, 1998
Issue release date: September 1998
Int Arch Allergy Immunol 1998;117:60–67

RANTES Production by Cytokine–Stimulated Nasal Fibroblasts: Its Inhibition by Glucocorticoids

Meyer J.E. · Berner I. · Teran L.M. · Bartels J. · Sticherling M. · Schröder J.M. · Maune S.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Nasal fibroblasts play an important role in both nasal polyposis and nasal allergic diseases and they are known to release a number of proinflammatory cytokines, including GM–CSF, IL–8 and IL–6. The aim of this present work was to investigate whether cytokine–stimulated nasal fibroblasts release biologically active RANTES as well as to study the effect of corticosteroids on the ability of nasal fibroblasts to produce the cytokine. Measurements of RANTES by ELISA demonstrated that RANTES is constitutively secreted spontaneously (21±4 vs. 19±6 ng/ml, respectively p>0.05). Stimulation of these cells with either TNF–α, IL–1β or IFN–γ induce further release of RANTES in a dose–dependent manner with TNF–α being the most potent stimulus. RANTES mRNA expression in nasal fibroblasts correlated with the amount of protein released in the culture supernatant upon cytokine stimulation. Moreover, chemotaxis studies demonstrated that the nasal–derived RANTES was biologically active on eosinophils. Betamethasone and hydrocortisone were found to downregulate RANTES mRNA expression in TNF–α–stimulated fibroblasts. These observations suggest that RANTES released by nasal fibroblasts may regulate eosinophil recruitment in nasal disease while glucocorticoids may inhibit the influx of these cells by suppressing the production of RANTES.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Flavahan NA, Slifman NR, Gleich GJ, Vanhoutte PM: Human eosinophil major basic protein causes hyperreactivity of respiratory smooth muscle. Role of the epithelium. Am Rev Respir Dis 1988;138:685–688.
  2. Hastie AT, Loegering DA, Gleich GJ: The effect of purified human eosinophil major cationic protein on mammalian ciliary activity. Am Rev Respir Dis 1987;135:685–688.
  3. Wong DT, Weller PF, Galli SJ, et al: Human eosinophils express transforming growth factor a. J Exp Med 1990;172:673–681.
  4. Ohno I, Lea RG, Flanders KC, et al: Eosinophils in chronically inflamed human upper airway tissue express transforming growth factor b1 gene (TGFb1). J Clin Invest 1992;89: 1662–1668.
  5. Rubbia–Brandt L, Sappino A, Gabbiani G: Locally applied GM–CSF induces the accumulation of a–smooth muscle actin containing myofibroblasts. Virchows Arch 1991;60:73–82.
  6. Wagenmann M, Dater I, Rudack I, Ganzer U, Bachert C: IL–5 synthesis is upregulated in human nasal polyp tissue. J Allergy Clin Immunol 1997;99:837–842.
  7. Ponath PD, Qin S, Ringier DJ, et al: Cloning of the human eosinophil chemoattractant, eotaxin. J Clin Invest 1996;97:604–612.
  8. Beck LA, Stellato C, Beall LD, et al: Detection of the chemokine RANTES and endothelial adhesion molecules in nasal polyps. J Allergy Clin Immunol 1996;98:766–780.
  9. Teran LM, Park H, Djukanovic R, Roberts K, Holgate ST: Cultured nasal polyps from nonatopic and atopic patients released RANTES spontaneously and after stimulation with phytohemagglutinin. J Allergy Clin Immunol 1997;100:499–504.
  10. Schall TJ: Biology of the RANTES/SIS cytokine family. Cytokine 1991;3:165–183.
  11. Teran LM, Davies DE: The chemokines: Their potential role in allergic inflammation. Clin Exp Allergy 1996;126:1005–1019.
  12. Meurer R, Van Riper G, Feeney W, et al: Formation of eosinophilic and monocytic intradermal inflammatory sites in the dog by injection of human RANTES but not human monocyte chemoattractant protein 1, human macrophage inflammatory protein 1 alpha, or human interleukin 8. J Exp Med 1993;178:1913–1921.

    External Resources

  13. Hamilos DL, Leung DYM, Wood R, et al: Eosinophil infiltration in non–allergic chronic hyperplastic sinusitis with nasal polypsis (CHS/NP) is associated with endothelial VCAM–1 upregulation and expression of TNF–alpha. Am J Respir Cell Mol Biol 1996; 15:443–450.
  14. Umbach B, Hennebach U: Changes in connective tissue metabolism in fibroblasts from nasal polyps. HNO 1994;42:344–349.
  15. Xing Z, Jordana M, Braciak T, Ohtoshi T, Gauldie J: Lypopolysaccaride induces expression of granulocyte macrophage colony–stimulating factor, interleukin–8, and interleukin–6 in human nasal, but not lung, fibroblasts: Evidence for heterogeneity within the respiratory tract. Am Respir Cell Mol Biol 1993;9:255– 263.
  16. Maune S, Berner I, Sticherling M, Kulke R, Bartels J, Schröder J–M: Fibroblasts but not nasal epithelial cells obtained from human nasal mucosa produce the chemokine RANTES. Rhinology 1997;34:210–214.
  17. Kameyoshi YA, Dorschener AI, Mallet E, et al: Cytokine RANTES released by thrombin–stimulated platelets is a potent attractant for human eosinophils. J Exp Med 1992;176:587– 592.
  18. Sticherling M, Kuepper M, Koltrowitz F, et al: Detection of chemokine RANTES in cytokine–stimulated human dermal fibroblasts. J Invest Dermatol 1995;105:585–591.
  19. Devergne O, Marfaing Koka A, Schall TJ, et al: Production of the RANTES chemokine in delayed–type hypersensitivity reactions: Involvement of macrophages and endothelial cells. J Exp Med 1994;179:1689–1694.
  20. Schall TJ, Jongstra J, Dyer BJ, et al: A human T–cell specific molecule is a member of a new gene family. J Immunol 1988;141:1018–1025.

    External Resources

  21. Chihara J, Oyamada H, Yamada H, et al: Expression of mRNA for RANTES in human eosinophils. Int Arch Allergy Immunol 1895; 114(suppl 1):33–35.
  22. Teran LM, Noso N, Carroll MP, et al: Eosinophil recruitment following allergen challenge is associated with the release of the chemokine RANTES in asthmatic airways. J Immunol 1996;157:1806–1812.
  23. Bradding P, Mediwake R, Feather IH, et al: TNF–alpha is localized to nasal mucosal mast cells and is released in acute allergic rhinitis. Clin Exp Allergy 1995;25:406–415.
  24. Sim TC, Reece LM, Hilsmeier KA, Grant JA, Alam R: Secretion of chemokines and other cytokines in allergen–induced nasal responses: Inhibition by topical steroid treatment. Am J Respir Crit Care Med 1995;152:927–933.
  25. Kwon OJ, Joes OP, Robbins RA, Schall TJ, Williams TJ, Barnes PJ: Glucocorticoid inhibition of RANTES expression in human lung epithelial cells. Am J Respir Cell Mol Biol 1995; 12:488–496.
  26. Stellato C, Beck LA, Gorgone GA, et al: Expression of the chemokine RANTES by a human bronchial epithelial cell line: Modulation by cytokines and glucocorticoids. J Immunol 1995;155:410–418.
  27. Kuschinsky G, Lüllmann H, Peters T: Kurzes Lehrbuch der Pharmakologie und Toxikologie. Stuttgart, Thieme, 1978, pp 277–278.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50