Apoptosis and apoptosis-related molecules in the submandibular gland of the nonobese diabetic mouse model for Sjögren's syndrome: limited role for apoptosis in the development of sialoadenitis.
Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the exocrine glands. Pathogenetic aspects of the disease can be studied in the nonobese diabetic (NOD) mouse strain, a spontaneous model for Sjögren's syndrome. Apoptosis may play a role in the initation phase and in the effector phase of autoimmune diseases. Here, we have examined the role of apoptosis in the development of sialoadenitis in the NOD mouse. Apoptotic cells and the expression of apoptosis-related molecules were studied in submandibular glands (SMG) of NOD and NOD-scid mice before and after the onset of sialoadenitis. Numbers of apoptotic cells were not increased as compared with control mice, at any age. By immunohistochemistry, we demonstrated increased expression of Fas, Fas ligand (FasL), and bcl-2 on SMG epithelial cells of NOD and NOD-scid mice, as early as 3 days of age. mRNA expression of Fas and FasL was also examined in SMG by RQ-PCR. Low-level expression of Fas and FasL mRNA was observed in all mouse strains, from 1 day of age onward. We conclude that increased protein expression of Fas and FasL on SMG epithelial cells of NOD and NOD-scid mice probably indicates a genetically programmed abnormality in these cells that may form a trigger for the development of sialoadenitis in NOD mice. Because increased numbers of apoptotic cells were not observed, a role for actual apoptosis in the initiation or effector phase of sialoadenitis in the NOD mouse is unlikely.
Van Blokland
Saskia C A
SC
Department of Immunology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands. vanblokland@immu.fgg.eur.nl
Van Helden-Meeuwsen
Cornelia G
CG
Wierenga-Wolf
Annet F
AF
Tielemans
Dennis
D
Drexhage
Hemmo A
HA
Van De Merwe
Joop P
JP
Homo-Delarche
Françoise
F
Versnel
Marjan A
MA
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D053222:Fas Ligand Protein; D005260:Female; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016133:Polymerase Chain Reaction; D012466:Salivary Gland Diseases / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000473:pathology*; D013363:Submandibular Gland / Q000473:pathology*; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor