Abstract
IntroductionProto-oncogene survivin is a member of the inhibitor of apoptosis (IAP) family of proteins. The presence of serous antibodies against survivin in patients with systemic sclerosis has been previously reported; however, there are few reports regarding the pathophysiological relationship between survivin and systemic sclerosis. We herein investigated the expression and function of survivin in SSc patients.MethodsWe performed immunohistochemistry analyses to determine the expression of XIAP, cIAP and survivin in skin lesions from patients with SSc and non-SSc. The expression levels of survivin in peripheral blood mononuclear cells (PBMCs) obtained from SSc patients and healthy controls were evaluated using RT-PCR and flow cytometry. Additionally, the function of survivin was verified with overexpression experiments using monocyte-derived dendritic cells (Mo-DCs).ResultsThe expression patterns of both XIAP and cIAP were similar, while only the survivin expression differed between the SSc and non-SSc skin lesions. Survivin-overexpressing cells were detected in the SSc dermis frequently. The positive rate of survivin in SSc dermis (64.3 %, 9/14) was higher than that in non-SSc dermis (11.2 %, 1/9). Furthermore, survivin+ cells expressed CD1a, one of the DC markers. Real-time PCR and FACS analyses revealed that the survivin-WT (wild type) expression levels in PBMCs, in particular CD14+ monocytes, from SSc patients were higher than that from healthy controls. Additionally, the overexpression experiments showed that survivin-WT-overexpressing CD1a+ Mo-DCs have the characteristics of promoting cell cycle progression and decreasing apoptotic cells.ConclusionsThese findings suggest that dermal survivin+ CD1a+ cell infiltration may be a potential biomarker of SSc skin lesions. PBMCs and monocytes from SSc patients also overexpressed survivin; therefore, dermal survivin+ DC may be derived from peripheral blood monocytes. Additionally, survivin may be involved in dermal CD1a+ DC proliferation through cell cycle activation and resistance to apoptosis. Survivin may be an important molecule for the pathogenesis of SSc.
Highlights
Proto-oncogene survivin is a member of the inhibitor of apoptosis (IAP) family of proteins
Real-time PCR and fluorescence-activated cell sorting (FACS) analyses revealed that the survivin-wild type (WT) expression levels in peripheral blood mononuclear cell (PBMC), in particular CD14+ monocytes, from Systemic sclerosis (SSc) patients were higher than that from healthy controls
These findings suggest that dermal survivin+ CD1a+ cell infiltration may be a potential biomarker of SSc skin lesions
Summary
Proto-oncogene survivin is a member of the inhibitor of apoptosis (IAP) family of proteins. Survivin is a member of the inhibitor of apoptosis (IAP) family of proteins, which is characterized by several baculovirus IAP repeat (BIR) domains [1, 2]. It is encoded by the baculoviral IAP repeat containing 5 (BIRC5) gene on human chromosome 17q25, which encodes a 16.5 kDa protein of 142 amino acids. Survivin plays pivotal roles in many fundamental cellular processes, including cell division and apoptosis [3], and has been suggested to be involved in Recently, it has been demonstrated that some autoimmune diseases (for example, rheumatoid arthritis and multiple sclerosis) are associated with IAP family proteins [7, 8].
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