| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Departments of Pathology*
and Pediatric
Dentistry,
Tokushima University School of Dentistry,
Tokushima, Japan
Estrogenic action has been suggested to be responsible for the
strong female preponderance of autoimmune diseases, but the
role of estrogens in the female has not been well characterized. We
evaluated the effects of estrogen deficiency in a murine model for
autoimmune exocrinopathy of Sjögren's syndrome (SS). Severe
destructive autoimmune lesions developed in the salivary and lacrimal
glands in estrogen-deficient mice, and these lesions were
recovered by estrogen administration. We detected an intense estrogen
receptor in splenic CD8+ T cells compared with that in
CD4+ T cells, and concanavalin-A-stimulated
blastogenesis of splenic CD8+ T cells with estrogens was
much higher than that of CD4+ T cells. We found a
significant increase in serum autoantibody production against the
organ-specific autoantigen 
-fodrin. Moreover, an increased
proportion of TUNEL+ apoptotic epithelial duct cells was
observed in estrogen-deficient mice. It was demonstrated that
Fas-mediated apoptosis in cultured salivary gland cells was clearly
inhibited by estrogens in vitro. These results indicate
that dysfunction of regulatory T cells by estrogen deficiency may play
a crucial role on acceleration of organ-specific autoimmune
lesions, and estrogenic action further influences target
epithelial cells through Fas-mediated apoptosis in a murine model for
SS.
This article has been cited by other articles:
 |
|
 |
|
  N. Ishimaru, R. Arakaki, F. Omotehara, K. Yamada, K. Mishima, I. Saito, and Y. Hayashi Novel Role for RbAp48 in Tissue-Specific, Estrogen Deficiency-Dependent Apoptosis in the Exocrine Glands Mol. Cell. Biol., April 15, 2006; 26(8): 2924 - 2935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Suzuki, F. Schirra, S. M. Richards, N. S. Treister, M. J. Lombardi, P. Rowley, R. V. Jensen, and D. A. Sullivan Estrogen's and Progesterone's Impact on Gene Expression in the Mouse Lacrimal Gland Invest. Ophthalmol. Vis. Sci., January 1, 2006; 47(1): 158 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Imamov, G.-J. Shim, M. Warner, and J.-A. Gustafsson Estrogen Receptor beta in Health and Disease Biol Reprod, November 1, 2005; 73(5): 866 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-J. Shim, M. Warner, H.-J. Kim, S. Andersson, L. Liu, J. Ekman, O. Imamov, M. E. Jones, E. R. Simpson, and J.-A. Gustafsson Aromatase-deficient mice spontaneously develop a lymphoproliferative autoimmune disease resembling Sjogren's syndrome PNAS, August 24, 2004; 101(34): 12628 - 12633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Maruyama, I. Saito, Y. Hayashi, E. Kompfner, R. I. Fox, D. R. Burton, and H. J. Ditzel Molecular Analysis of the Human Autoantibody Response to {alpha}-Fodrin in Sjogren's Syndrome Reveals Novel Apoptosis-Induced Specificity Am. J. Pathol., July 1, 2004; 165(1): 53 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-J. Shim, L. L. Kis, M. Warner, and J.-A. Gustafsson Autoimmune glomerulonephritis with spontaneous formation of splenic germinal centers in mice lacking the estrogen receptor alpha gene PNAS, February 10, 2004; 101(6): 1720 - 1724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ishimaru, R. Arakaki, M. Watanabe, M. Kobayashi, K. Miyazaki, and Y. Hayashi Development of Autoimmune Exocrinopathy Resembling Sjogren's Syndrome in Estrogen-Deficient Mice of Healthy Background Am. J. Pathol., October 1, 2003; 163(4): 1481 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Saegusa, N. Ishimaru, K. Yanagi, K. Mishima, R. Arakaki, T. Suda, I. Saito, and Y. Hayashi Prevention and Induction of Autoimmune Exocrinopathy Is Dependent on Pathogenic Autoantigen Cleavage in Murine Sjogren's Syndrome J. Immunol., July 15, 2002; 169(2): 1050 - 1057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Inoue, K. Tsubota, M. Ono, Y. Kizu, F. Mizuno, K. Takada, K. Yamada, K. Yanagi, Y. Hayashi, and I. Saito Possible Involvement of EBV-Mediated {{alpha}}-Fodrin Cleavage for Organ-Specific Autoantigen in Sjogren's Syndrome J. Immunol., May 1, 2001; 166(9): 5801 - 5809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I Toda, M Kuwana, K Tsubota, and Y Kawakami Lack of evidence for an increased microchimerism in the circulation of patients with Sjogren's syndrome Ann Rheum Dis, March 1, 2001; 60(3): 248 - 253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tsubota, H. Fujita, K. Tadano, T. Takeuchi, T. Murakami, I. Saito, and Y. Hayashi Improvement of Lacrimal Function by Topical Application of CyA in Murine Models of Sjogren's Syndrome Invest. Ophthalmol. Vis. Sci., January 1, 2001; 42(1): 101 - 110. [Abstract] [Full Text]
|
|
|
|
|
|
N. Ishimaru, T. Yoneda, K. Saegusa, K. Yanagi, N. Haneji, K. Moriyama, I. Saito, and Y. Hayashi Severe Destructive Autoimmune Lesions with Aging in Murine Sjogren's Syndrome through Fas-Mediated Apoptosis Am. J. Pathol., May 1, 2000; 156(5): 1557 - 1564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Garza, S. S. Agersborg, E. Baker, and K. S. K. Tung Persistence of Physiological Self Antigen Is Required for the Regulation of Self Tolerance J. Immunol., April 15, 2000; 164(8): 3982 - 3989. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
