The Journal of Experimental Medicine
ELISpot, FluoroSpot and ELISA kits from Mabtech
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 5 February 2001.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 521K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Walter, M. J.
Right arrow Articles by Holtzman, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Walter, M. J.
Right arrow Articles by Holtzman, M. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/2001/2/339/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 3, February 5, 2001 339-352

Original Article

Interleukin 12 P40 Production by Barrier Epithelial Cells during Airway Inflammation

Michael J. Waltera, Naohiro Kajiwaraa, Peter Karanjaa, Mario Castroa, and Michael J. Holtzmana,b

a Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110
b Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri 63110
Washington University School of Medicine, Box 8052, 660 South Euclid Ave., St. Louis, MO 63110.314-362-8987314-362-8970

holtzmanm{at}msnotes.wustl.edu

Human airway epithelial cells appear specially programmed for expression of immune response genes implicated in immunity and inflammation. To better determine how this epithelial system operates in vivo, we analyzed its behavior in mouse models that allow for in vitro versus in vivo comparison and genetic modification. Initial comparisons indicated that tumor necrosis factor {alpha} induction of epithelial intercellular adhesion molecule 1 required sequential induction of interleukin (IL)-12 (p70) and interferon {gamma}, and unexpectedly localized IL-12 production to airway epithelial cells. Epithelial IL-12 was also inducible during paramyxoviral bronchitis, but in this case, initial IL-12 p70 expression was followed by 75-fold greater expression of IL-12 p40 (as monomer and homodimer). Induction of IL-12 p40 was even further increased in IL-12 p35-deficient mice, and in this case, was associated with increased mortality and epithelial macrophage accumulation. The results placed epithelial cell overgeneration of IL-12 p40 as a key intermediate for virus-inducible inflammation and a candidate for epithelial immune response genes that are abnormally programmed in inflammatory disease. This possibility was further supported when we observed IL-12 p40 overexpression selectively in airway epithelial cells in subjects with asthma and concomitant increases in airway levels of IL-12 p40 (as homodimer) and airway macrophages. Taken together, these results suggest a novel role for epithelial-derived IL-12 p40 in modifying the level of airway inflammation during mucosal defense and disease.

Key Words: asthma • cell adhesion molecule • mucosal immunity • paramyxoviral bronchitis • macrophage

Abbreviations used in this paper: ANOVA, analysis of variance; BAL, bronchoalveolar lavage; EID50, 50% egg infectious dose; ICAM, intercellular adhesion molecule; mTE, mouse tracheal epithelial; NF, nuclear factor; RANTES, regulated upon activation, normal T cell expressed and secreted; SdV, Sendai virus.

© 2001 The Rockefeller University Press


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS