Possible involvement of EBV-mediated alpha-fodrin cleavage for organ-specific autoantigen in Sjogren's syndrome.
A cleavage product of alpha-fodrin may be an important organ-specific autoantigen in the pathogenesis of Sjogren's syndrome (SS), but the mechanisms of alpha-fodrin cleavage remain unclear. Since EBV has been implicated in the pathogenesis of SS, we determined whether EBV activation could induce the SS-specific 120-kDa autoantigen alpha-fodrin. ZEBRA mRNA expression, a marker for activation of the lytic cycle of EBV, was found in the salivary gland tissues from SS patients, but not in those from control individuals. ZEBRA-expressing lymphoid cells were also found in the SS glands in double-stained immunohistochemistry. Furthermore, a significant link between production of Abs against 120-kDa alpha-fodrin and reactivated EBV Ag was found in sera from patients with SS, but not in those from control individuals. EBV-activated lymphoid cells showed specific alpha-fodrin cleavage to the expected 120-kDa fragments in vitro. Pretreatment with caspase inhibitors inhibited cleavage of alpha-fodrin. Thus, an increase in apoptotic protease activities induced by EBV reactivation may be involved in the progression of alpha-fodrin proteolysis in the development of SS.
Inoue
H
H
Department of Pathology, Tokushima University School of Dentistry, Tokushima, Japan.
Tsubota
K
K
Ono
M
M
Kizu
Y
Y
Mizuno
F
F
Takada
K
K
Yamada
K
K
Yanagi
K
K
Hayashi
Y
Y
Saito
I
I
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D007611:Aprotinin / Q000494:pharmacology; D001324:Autoantigens / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D006868:Hydrolysis; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D008970:Molecular Weight; D009928:Organ Specificity / Q000276:immunology; D010436:Pepstatins / Q000494:pharmacology; D012859:Sjogren's Syndrome / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D015534:Trans-Activators / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis; D014775:Virus Activation / Q000276:immunology; D013049:Spectrin
D000590:Amino Acid Chloromethyl Ketones; D007611:Aprotinin; D001324:Autoantigens; D002352:Carrier Proteins; D020169:Caspases; D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; D007930:Leucine; D007976:Leupeptins; D008840:Microfilament Proteins; D010436:Pepstatins; D015534:Trans-Activators; D014764:Viral Proteins; D013049:Spectrin; C063676:BZLF1 protein, Herpesvirus 4, Human; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C014195:Streptomyces pepsin inhibitor; C012211:ubenimex; C032854:leupeptin; C024974:E 64; C031375:pepstatin