Pathological survivin expression links viral infections with pathogenesis of erosive rheumatoid arthritis.
Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage and bone destruction. Insufficient apoptosis in the inflamed RA synovium along with accumulation of highly differentiated B- and T-lymphocytes as well as invasive growth of macrophages and fibroblasts is among the major mechanisms supporting joint destruction. We have recently shown that circulating survivin, an apoptosis inhibitor tightly bound to tumorigenesis, is an independent predictor of development and progression of joint destruction in RA. In this review we discuss the possible connectivity between viral infection, leading to interferon (IFN)-alpha production, survivin expression, and subsequent joint inflammation. The role of IFN-alpha and the involvement of IFN transcription factors and phosphoinositide-3-kinase signalling as essential modulators of arthritogenic process are discussed in the context of survivin.
Bokarewa
M
M
Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, Göteborg University, S-41346 Göteborg, Sweden. maria.bokarewa@rheuma.gu.se
Tarkowski
A
A
Magnusson
M
M
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D012190:Retroviridae / Q000472:pathogenicity; D012192:Retroviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000077022:Survivin; D014412:Tumor Virus Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin