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CD1a+ survivin+ dendritic cell infiltration in dermal lesions of systemic sclerosis.

Mokuda S, Miyazaki T, Ubara Y, Kanno M, Sugiyama E, Takasugi K, Masumoto J - Arthritis Res. Ther. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. sho-mokuda@hiroshima-u.ac.jp.

ABSTRACT

Introduction: Proto-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.

Methods: We 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).

Results: The 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.

Conclusions: These 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.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemistry (IHC) staining of XIAP, cIAP and survivin in systemic sclerosis (SSc) dermal lesions. SSc (a, c, e) and non-SSc (b, d, f) skin lesions evaluated with IHC (all stained by red, ×20). The SSc patients were designated numbers 4, 6, 7, and 12 in Table 1 (n = 4). A case of rheumatoid arthritis (RA), a case of polymyositis/dermatomyositis (PM/DM) and two cases of osteoarthritis (OA) were included among the non-SSc patients (n = 4). a, b XIAP. c, d cIAP. e, f survivin. Representative images are shown. In the dermis of SSc, many survivin-positive cells were detected (arrows)
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Fig1: Immunohistochemistry (IHC) staining of XIAP, cIAP and survivin in systemic sclerosis (SSc) dermal lesions. SSc (a, c, e) and non-SSc (b, d, f) skin lesions evaluated with IHC (all stained by red, ×20). The SSc patients were designated numbers 4, 6, 7, and 12 in Table 1 (n = 4). A case of rheumatoid arthritis (RA), a case of polymyositis/dermatomyositis (PM/DM) and two cases of osteoarthritis (OA) were included among the non-SSc patients (n = 4). a, b XIAP. c, d cIAP. e, f survivin. Representative images are shown. In the dermis of SSc, many survivin-positive cells were detected (arrows)

Mentions: We first investigated the expressions of several IAP proteins in SSc and non-SSc skin lesions using IHC. The expression patterns of both XIAP and cIAP were similar (Fig. 1a-d), while only the survivin expression differed between SSc and non-SSc skin lesions (Fig. 1e-f). Survivin-overexpressing cells were detected in SSc dermis frequently. Subsequently, we performed the IHC analyses using anti-survivin antibodies on skin specimens obtained from 14 SSc patients and nine non-SSc patients (five cases of RA, one case of PM/DM and three cases of OA). Survivin-positive small cells were detected in the SSc dermal lesions. These cells were detected in the SSc dermis in 64.3 % of the cases (9/14), while they were rarely detected in the dermis from non-SSc patients (11.1 %, 1/9 cases) (p = 0.017) (Fig. 2a) (Table 1). Moreover, the rate of the coexistence of organ involvement in dermal survivin-positive SSc patients (62.5 %, 6/9) (three cases with interstitial pneumonia (IP), two cases with renal crisis (RC) and one case with coexisting RC and pulmonary artery hypertension (PAH)) was higher than that in dermal survivin-negative SSc patients (0 %, 0/5) (p = 0.028). Consequently, the dermal survivin may be a potential diagnostic marker of SSc with organ derangement.Fig. 1


CD1a+ survivin+ dendritic cell infiltration in dermal lesions of systemic sclerosis.

Mokuda S, Miyazaki T, Ubara Y, Kanno M, Sugiyama E, Takasugi K, Masumoto J - Arthritis Res. Ther. (2015)

Immunohistochemistry (IHC) staining of XIAP, cIAP and survivin in systemic sclerosis (SSc) dermal lesions. SSc (a, c, e) and non-SSc (b, d, f) skin lesions evaluated with IHC (all stained by red, ×20). The SSc patients were designated numbers 4, 6, 7, and 12 in Table 1 (n = 4). A case of rheumatoid arthritis (RA), a case of polymyositis/dermatomyositis (PM/DM) and two cases of osteoarthritis (OA) were included among the non-SSc patients (n = 4). a, b XIAP. c, d cIAP. e, f survivin. Representative images are shown. In the dermis of SSc, many survivin-positive cells were detected (arrows)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4588499&req=5

Fig1: Immunohistochemistry (IHC) staining of XIAP, cIAP and survivin in systemic sclerosis (SSc) dermal lesions. SSc (a, c, e) and non-SSc (b, d, f) skin lesions evaluated with IHC (all stained by red, ×20). The SSc patients were designated numbers 4, 6, 7, and 12 in Table 1 (n = 4). A case of rheumatoid arthritis (RA), a case of polymyositis/dermatomyositis (PM/DM) and two cases of osteoarthritis (OA) were included among the non-SSc patients (n = 4). a, b XIAP. c, d cIAP. e, f survivin. Representative images are shown. In the dermis of SSc, many survivin-positive cells were detected (arrows)
Mentions: We first investigated the expressions of several IAP proteins in SSc and non-SSc skin lesions using IHC. The expression patterns of both XIAP and cIAP were similar (Fig. 1a-d), while only the survivin expression differed between SSc and non-SSc skin lesions (Fig. 1e-f). Survivin-overexpressing cells were detected in SSc dermis frequently. Subsequently, we performed the IHC analyses using anti-survivin antibodies on skin specimens obtained from 14 SSc patients and nine non-SSc patients (five cases of RA, one case of PM/DM and three cases of OA). Survivin-positive small cells were detected in the SSc dermal lesions. These cells were detected in the SSc dermis in 64.3 % of the cases (9/14), while they were rarely detected in the dermis from non-SSc patients (11.1 %, 1/9 cases) (p = 0.017) (Fig. 2a) (Table 1). Moreover, the rate of the coexistence of organ involvement in dermal survivin-positive SSc patients (62.5 %, 6/9) (three cases with interstitial pneumonia (IP), two cases with renal crisis (RC) and one case with coexisting RC and pulmonary artery hypertension (PAH)) was higher than that in dermal survivin-negative SSc patients (0 %, 0/5) (p = 0.028). Consequently, the dermal survivin may be a potential diagnostic marker of SSc with organ derangement.Fig. 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. sho-mokuda@hiroshima-u.ac.jp.

ABSTRACT

Introduction: Proto-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.

Methods: We 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).

Results: The 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.

Conclusions: These 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.

No MeSH data available.


Related in: MedlinePlus