| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Articles |
Institute of Anatomy and Cell Biology, Sahlgrenska Academy at Goteborg University, Box 420, 40530 Goteborg, Sweden. sofia.tedelind@anatcell.gu.se
OBJECTIVE: Proinflammatory cytokines are known to affect the follicular epithelium in autoimmune thyroid disease. Here we investigated the effect of interferon-gamma (IFN-gamma) on the barrier function of primary cultured human thyrocytes. DESIGN: Graves' thyroid follicle segments were cultured as a tight and polarised monolayer on the filter of a bicameral chamber, thereby allowing the in vivo epithelial characteristics to be maintained. METHODS: Transepithelial electrical resistance was measured with a Millicell ERS ohmmeter. The tight junction proteins claudin-1 and occludin were analysed by immunofluorescence and Western blotting. Cell morphology was studied by transmission electron microscopy. RESULTS: Thyrotrophin (TSH; 1 mU/ml) promoted the development of a tight epithelium monitored as a persistent increase in the transepithelial resistance to about 800 omega x cm2. IFN-gamma (100 U/ml), on the other hand, decreased the resistance to 60-150 omega x cm2 after 48 h. In IFN-gamma-treated cells the expression of claudin-1, but not that of occludin, was decreased along with a diminished intracellular and cell surface immunostaining. In addition, claudin-1 was disrupted at cell-cell contacts. IFN-gamma also caused profound cell shape changes and a multilayered cellular organisation, without ultrastructural or biochemical (caspase-3 activity) signs of cytotoxicity. TSH was unable to counteract the effects of IFN-gamma. CONCLUSIONS: IFN-gamma destroys the barrier function of filter-cultured human thyroid epithelial cells. The loss of barrier involves down-regulation and an altered distribution of claudin-1. This novel effect of IFN-gamma on target cells in thyroid autoimmunity might be of pathophysiological relevance to the exposure of hidden autoantigens.
This article has been cited by other articles:
|
|
 |
|
  O. J. Baker, J. M. Camden, R. S. Redman, J. E. Jones, C. I. Seye, L. Erb, and G. A. Weisman Proinflammatory cytokines tumor necrosis factor-{alpha} and interferon-{gamma} alter tight junction structure and function in the rat parotid gland Par-C10 cell line Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1191 - C1201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Howe, C. Reardon, A. Wang, A. Nazli, and D. M. McKay Transforming Growth Factor-{beta} Regulation of Epithelial Tight Junction Proteins Enhances Barrier Function and Blocks Enterohemorrhagic Escherichia coli O157:H7-Induced Increased Permeability Am. J. Pathol., December 1, 2005; 167(6): 1587 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Watson, C. J. Hoare, D. R. Garrod, G. L. Carlson, and G. Warhurst Interferon-{gamma} selectively increases epithelial permeability to large molecules by activating different populations of paracellular pores J. Cell Sci., November 15, 2005; 118(22): 5221 - 5230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Turksen and T.-C. Troy Barriers built on claudins J. Cell Sci., May 15, 2004; 117(12): 2435 - 2447. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
