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Therapeutic and immunomodulatory effects of adipose-derived stromal cells on psoriasis animal model
Abstracts from the 41st Annual Meeting / Journal of Dermatological Science 86 (2017) e1–e95
ever, its relationship with pruritus and severity of AD remains unclear. In the present study, we assessed the relationships among plasma GzmB level, pruritus and severity score in patients with AD. Plasma GzmB level was significantly higher in patients with AD and psoriasis than in healthy controls. In contrast, plasma GzmA level did not differ significantly between patients with AD and psoriasis, and healthy controls. Pruritus visual analogue scale (VAS) score correlated positively with plasma GzmB level in AD patients. Correlation analyses also showed that plasma GzmB level was positively correlated with scoring atopic dermatitis (SCORAD) in AD patients, but there was no correlation among GzmB level, VAS score, psoriasis area or severity index (PASI) in patients with psoriasis. Plasma concentration of gastrin releasing peptide (GRP), itch-mediating peptide, was higher in patients with AD than in healthy controls, and was positively correlated with VAS score and plasma GzmB level. These data suggest that plasma GzmB level may indicate severity of both pruritus and dermatitis in AD patients. http://dx.doi.org/10.1016/j.jdermsci.2017.02.030 2015 JSID’s Fellowship Shiseido Award The ex vivo-induced regulatory B cells ameliorate tissue fibrosis and autoimmunity via an anti-oxidative effect in systemic sclerosis Ayumi Yoshizaki ∗ , Takemichi Fukasawa, Satoshi Ebata, Shinichi Sato Department of Dermatology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan Purpose: Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular damage and tissue fibrosis on an autoimmune background. Although the pathogenesis of SSc remains unknown, it has been proposed that oxidative stress play an important role in disease development. Many previous studies have confirmed that production of free radicals is enhanced in human SSc patients, due to ischemia and reperfusion injury following Raynaud’s phenomenon. Furthermore, we previously demonstrated that in bleomycin (BLM)-induced SSc model mice, the production of free radicals from inflammatory cells affects tissue fibrosis and autoimmunity. Recent studies indicated that regulatory B cells ameliorate several autoimmune diseases. However, the relationship between oxidative stress and regulatory B cells remains totally unclear. Methods: The ex vivo-induced regulatory B cells, which we established previously, were adoptively transferred BLM-induced SSc model mice. Then, serum levels of 8-isoprostane, a marker of oxidative stress, were measured. Furthermore, we assessed skin and lung fibrosis histologically. Protein and mRNA levels of profibrogenic cytokines were measured. Results: The ex vivo-induced regulatory B cells reduced skin and lung fibrosis and profibrogenic cytokine production in BLMinduced SSc model mice. Especially, serum levels of 8-isoprostane were decreased by adoptively transferred ex vivo-induced regulatory B cells. Furthermore, ex vivo-induced regulatory B cells significantly inhibited free radical production from inflammatory cells cultured with BLM. Conclusion: These results suggest that the ex vivo-induced regulatory B cells inhibited free radical production from inflammatory cells, results in ameliorating the disease manifestations of SSc. http://dx.doi.org/10.1016/j.jdermsci.2017.02.031
e11
P01-29[O1-11] Therapeutic and immunomodulatory effects of adipose-derived stromal cells on psoriasis animal model Yasushi Matsuzaki ∗ , Akiko Rokunohe, Daiki Rokunohe, Eiko Makita, Hajime Nakano, Daisuke Sawamura Department of Dermatology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan Background: Adipose-derived stromal cell (ASC)-based therapies have recently been considered useful for skin disorders such as skin wounds/defects and inflammatory disorders. However, the effects of ASCs on psoriasis have not been investigated. Objective: We verified whether the administration of autogenic ASCs could suppress an over-activated immune system, and discovered clues regarding the improvement of psoriasis. Methods: We applied imiquimod (IMQ) cream to shaved dorsal skin of mice for 5 consecutive days. On days 0, 2, and 4, either ASCs or PBS was injected into dorsal intradermal areas. On day 6, mice were sacrificed for skin and blood sample collection. Levels of inflammatory factors such as IL-17A and TNF-alpha were evaluated by ELISA and qRT-PCR. Results: Three days after IMQ application, dorsal skin treated with IMQ and PBS began to display signs of erythema, scaling and thickening. In contrast, dorsal skin treated with IMQ and ASCs exhibited slight erythema on day 6, indicating that ASCs predominantly inhibit IMQ-induced inflammatory changes in murine skin. Histological examination revealed that ASCs injection significantly inhibited IMQ-induced psoriatic inflammatory changes. Furthermore, IMQ-induced splenomegaly was markedly improved by intradermal ASC injection. Serum IL-17A and TNF-alpha levels were significantly lower in ASC-injected mice than in PBS-injected mice, indicating that intradermal skin application of ASCs definitely inhibited both regional psoriatic and systemic IMQ-induced inflammation. Conclusion: We demonstrated the immunosuppressive effects of ASCs in an IMQ-induced inflammatory environment. Additionally, we verified the potential clinical application of autogenic or allogeneic ASCs for the treatment of psoriasis. http://dx.doi.org/10.1016/j.jdermsci.2017.02.032 P01-30[O1-12] ␣2AP regulates vascular alteration by inhibiting VEGF signaling in systemic sclerosis Yosuke Kanno 1,∗ , En Shu 2 , Hiroyuki Kanoh 2 , Ayaka Matsuda 1 , Mariko Seishima 2 1
Doshisha Women Collage of Liberal Arts, Japan Gifu University Graduate School of Medicine, Japan Systemic sclerosis (SSc) is a connective tissues disease of unknown origin characterized by vascular damages and extensive fibrosis. Recently, we demonstrated that ␣2-antiplasmin (␣2AP) is associated with the development of fibrosis in SSc. We herein investigated the roles of ␣2AP on vascular dysfunction in SSc. The administration of ␣2AP induced vascular damages, such as the reduction of blood vessels and blood flow in mice. Conversely, the ␣2AP neutralization improved vascular damages in the bleomycin-induced mouse models of SSc. Additionally, we showed that the SSc fibroblasts conditioned media (CM) induced the reduction of tube formation, cell proliferation, and endothelial-junction-associated proteins (VE-cadherin and PECAM1) production in vascular endothelial cells (ECs), and 2
ever, its relationship with pruritus and severity of AD remains unclear. In the present study, we assessed the relationships among plasma GzmB level, pruritus and severity score in patients with AD. Plasma GzmB level was significantly higher in patients with AD and psoriasis than in healthy controls. In contrast, plasma GzmA level did not differ significantly between patients with AD and psoriasis, and healthy controls. Pruritus visual analogue scale (VAS) score correlated positively with plasma GzmB level in AD patients. Correlation analyses also showed that plasma GzmB level was positively correlated with scoring atopic dermatitis (SCORAD) in AD patients, but there was no correlation among GzmB level, VAS score, psoriasis area or severity index (PASI) in patients with psoriasis. Plasma concentration of gastrin releasing peptide (GRP), itch-mediating peptide, was higher in patients with AD than in healthy controls, and was positively correlated with VAS score and plasma GzmB level. These data suggest that plasma GzmB level may indicate severity of both pruritus and dermatitis in AD patients. http://dx.doi.org/10.1016/j.jdermsci.2017.02.030 2015 JSID’s Fellowship Shiseido Award The ex vivo-induced regulatory B cells ameliorate tissue fibrosis and autoimmunity via an anti-oxidative effect in systemic sclerosis Ayumi Yoshizaki ∗ , Takemichi Fukasawa, Satoshi Ebata, Shinichi Sato Department of Dermatology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan Purpose: Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular damage and tissue fibrosis on an autoimmune background. Although the pathogenesis of SSc remains unknown, it has been proposed that oxidative stress play an important role in disease development. Many previous studies have confirmed that production of free radicals is enhanced in human SSc patients, due to ischemia and reperfusion injury following Raynaud’s phenomenon. Furthermore, we previously demonstrated that in bleomycin (BLM)-induced SSc model mice, the production of free radicals from inflammatory cells affects tissue fibrosis and autoimmunity. Recent studies indicated that regulatory B cells ameliorate several autoimmune diseases. However, the relationship between oxidative stress and regulatory B cells remains totally unclear. Methods: The ex vivo-induced regulatory B cells, which we established previously, were adoptively transferred BLM-induced SSc model mice. Then, serum levels of 8-isoprostane, a marker of oxidative stress, were measured. Furthermore, we assessed skin and lung fibrosis histologically. Protein and mRNA levels of profibrogenic cytokines were measured. Results: The ex vivo-induced regulatory B cells reduced skin and lung fibrosis and profibrogenic cytokine production in BLMinduced SSc model mice. Especially, serum levels of 8-isoprostane were decreased by adoptively transferred ex vivo-induced regulatory B cells. Furthermore, ex vivo-induced regulatory B cells significantly inhibited free radical production from inflammatory cells cultured with BLM. Conclusion: These results suggest that the ex vivo-induced regulatory B cells inhibited free radical production from inflammatory cells, results in ameliorating the disease manifestations of SSc. http://dx.doi.org/10.1016/j.jdermsci.2017.02.031
e11
P01-29[O1-11] Therapeutic and immunomodulatory effects of adipose-derived stromal cells on psoriasis animal model Yasushi Matsuzaki ∗ , Akiko Rokunohe, Daiki Rokunohe, Eiko Makita, Hajime Nakano, Daisuke Sawamura Department of Dermatology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan Background: Adipose-derived stromal cell (ASC)-based therapies have recently been considered useful for skin disorders such as skin wounds/defects and inflammatory disorders. However, the effects of ASCs on psoriasis have not been investigated. Objective: We verified whether the administration of autogenic ASCs could suppress an over-activated immune system, and discovered clues regarding the improvement of psoriasis. Methods: We applied imiquimod (IMQ) cream to shaved dorsal skin of mice for 5 consecutive days. On days 0, 2, and 4, either ASCs or PBS was injected into dorsal intradermal areas. On day 6, mice were sacrificed for skin and blood sample collection. Levels of inflammatory factors such as IL-17A and TNF-alpha were evaluated by ELISA and qRT-PCR. Results: Three days after IMQ application, dorsal skin treated with IMQ and PBS began to display signs of erythema, scaling and thickening. In contrast, dorsal skin treated with IMQ and ASCs exhibited slight erythema on day 6, indicating that ASCs predominantly inhibit IMQ-induced inflammatory changes in murine skin. Histological examination revealed that ASCs injection significantly inhibited IMQ-induced psoriatic inflammatory changes. Furthermore, IMQ-induced splenomegaly was markedly improved by intradermal ASC injection. Serum IL-17A and TNF-alpha levels were significantly lower in ASC-injected mice than in PBS-injected mice, indicating that intradermal skin application of ASCs definitely inhibited both regional psoriatic and systemic IMQ-induced inflammation. Conclusion: We demonstrated the immunosuppressive effects of ASCs in an IMQ-induced inflammatory environment. Additionally, we verified the potential clinical application of autogenic or allogeneic ASCs for the treatment of psoriasis. http://dx.doi.org/10.1016/j.jdermsci.2017.02.032 P01-30[O1-12] ␣2AP regulates vascular alteration by inhibiting VEGF signaling in systemic sclerosis Yosuke Kanno 1,∗ , En Shu 2 , Hiroyuki Kanoh 2 , Ayaka Matsuda 1 , Mariko Seishima 2 1
Doshisha Women Collage of Liberal Arts, Japan Gifu University Graduate School of Medicine, Japan Systemic sclerosis (SSc) is a connective tissues disease of unknown origin characterized by vascular damages and extensive fibrosis. Recently, we demonstrated that ␣2-antiplasmin (␣2AP) is associated with the development of fibrosis in SSc. We herein investigated the roles of ␣2AP on vascular dysfunction in SSc. The administration of ␣2AP induced vascular damages, such as the reduction of blood vessels and blood flow in mice. Conversely, the ␣2AP neutralization improved vascular damages in the bleomycin-induced mouse models of SSc. Additionally, we showed that the SSc fibroblasts conditioned media (CM) induced the reduction of tube formation, cell proliferation, and endothelial-junction-associated proteins (VE-cadherin and PECAM1) production in vascular endothelial cells (ECs), and 2