PMID- 10393849
OWN - NLM
STAT- MEDLINE
DCOM- 19990726
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 155
IP  - 1
DP  - 1999 Jul
TI  - Estrogen deficiency accelerates autoimmune exocrinopathy in murine Sjogren's
      syndrome through fas-mediated apoptosis.
PG  - 173-81
AB  - 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 Sjogren'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 alpha-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.
FAU - Ishimaru, N
AU  - Ishimaru N
AD  - Departments of Pathology and Pediatric Dentistry, Tokushima University School of 
      Dentistry, Tokushima, Japan.
FAU - Saegusa, K
AU  - Saegusa K
FAU - Yanagi, K
AU  - Yanagi K
FAU - Haneji, N
AU  - Haneji N
FAU - Saito, I
AU  - Saito I
FAU - Hayashi, Y
AU  - Hayashi Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Estrogens)
RN  - 0 (fas Receptor)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Autoimmune Diseases/*etiology/pathology
MH  - B-Lymphocytes/physiology
MH  - Estrogens/*deficiency/pharmacology
MH  - Exocrine Glands/*immunology/pathology
MH  - Female
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Ovariectomy
MH  - Sjogren's Syndrome/*complications
MH  - T-Lymphocytes/physiology
MH  - Thymectomy
MH  - fas Receptor/*physiology
PMC - PMC1866653
EDAT- 1999/07/08 00:00
MHDA- 1999/07/08 00:01
CRDT- 1999/07/08 00:00
PHST- 1999/07/08 00:00 [pubmed]
PHST- 1999/07/08 00:01 [medline]
PHST- 1999/07/08 00:00 [entrez]
AID - S0002-9440(10)65111-5 [pii]
AID - 10.1016/S0002-9440(10)65111-5 [doi]
PST - ppublish
SO  - Am J Pathol. 1999 Jul;155(1):173-81. doi: 10.1016/S0002-9440(10)65111-5.