Objective Psoriasis is an immune-mediated inflammatory disease.Despite advances in the study of its pathogenesis,the exact development mechanism of psoriasis remains to be fully elucidated.Hyperproliferative epidermis...Objective Psoriasis is an immune-mediated inflammatory disease.Despite advances in the study of its pathogenesis,the exact development mechanism of psoriasis remains to be fully elucidated.Hyperproliferative epidermis plays a crucial role in psoriasis.This study aimed to investigate the effects of interleukin-36β(IL-36β)on keratinocyte dysfunction in vitro.Methods Human keratinocyte cell lines,HaCaT cells,were treated with 0(control),50 or 100 ng/ml IL-36βrespectively for 24 h.Cell viability was determined with a cell counting kit-8 assay.Flow cytometry was used to assess the effects of IL-36βon apoptosis and cell cycle distribution.Expressions of the differentiation markers,such as keratin 10 and involucrin,were evaluated by quantitative real-time polymerase chain reaction(RT-qPCR).Expressions of the inflammatory cytokines,IL-1βand IL-6 were tested by ELISA.Results CCK8 assay showed the survival rate had no significant difference between the control and treated group(P>0.05).Flow cytometry analysis showed cell cycle arrest at S phase in the IL-36β-treated groups compared with the control group(P<0.05).RT-qPCR verified the decreased mRNA expressions of keratin 10 and involucrin in the IL-36β-treated groups compared with the negative control(P<0.01).ELISA showed 100 ng/ml IL-36βenhanced levels of IL-1βand IL-6 in culture supernatants of HaCaT cells compared with the negative control(P<0.05).Conclusion Taken together,these findings suggest that IL-36βcould induce cell cycle arrest at S phase,inhibit keratin 10 and involucrin expressions and promote inflammatory activity in HaCaT cell lines.展开更多
Summary： This study examined the correlation of the expression of interleukin-36 （IL-36）, a novel member of interleukin-1 （IL-1） family, with p38 mitogen-activated protein kinase （p38 MAPK） and nu clear factor-...Summary： This study examined the correlation of the expression of interleukin-36 （IL-36）, a novel member of interleukin-1 （IL-1） family, with p38 mitogen-activated protein kinase （p38 MAPK） and nu clear factor-kappa B （NF-kB） pathways in psoriasis vulgaris skin lesions. The expression levels of IL-36a, IL-3613, IL-367, phosphorylated p38 MAPK, and NF-id3p65 were detected in the skin tissues of 38 psoriasis patients and 17 healthy control subjects by real-time quantitative reverse transcription po lymerase chain reaction （qRT-PCR） and Western blotting. The cytokine expression levels were com pared between the psoriasis group and the control group. A correlation analysis between cytokine pro teins was performed in the psoriasis group. Results showed that the expression levels of IL-36a, IL-3613, IL-36y, phosphorylated p38 MAPK and NF-rh3p65 in the psoriasis group were Significantly higher than those in the control group （P〈0.001）. In the psoriasis group, the IL-36 cytokine expression was positively correlated with phosphorylated p38 MAPK and NF-kBp65 expression （P〈0.05）. A significant positive correlation was also found between the phosphorylated p38 MAPK and NF-v,.Bp65 expression （P〈0.01）. It was concluded that the increased IL-36 expression is correlated with p38 MAPK and NF-kB pathways in psoriasis vulgaris skin lesions. All the three factors may be jointly involved in the pathogenesis and local inflammatory response of psoriasis.展开更多
基金Supported by the National Natural Science Foundation of China(No.81773331)CAMS Initiative for Innovative Medicine(No.2017-I2M-B&R-01)
文摘Objective Psoriasis is an immune-mediated inflammatory disease.Despite advances in the study of its pathogenesis,the exact development mechanism of psoriasis remains to be fully elucidated.Hyperproliferative epidermis plays a crucial role in psoriasis.This study aimed to investigate the effects of interleukin-36β(IL-36β)on keratinocyte dysfunction in vitro.Methods Human keratinocyte cell lines,HaCaT cells,were treated with 0(control),50 or 100 ng/ml IL-36βrespectively for 24 h.Cell viability was determined with a cell counting kit-8 assay.Flow cytometry was used to assess the effects of IL-36βon apoptosis and cell cycle distribution.Expressions of the differentiation markers,such as keratin 10 and involucrin,were evaluated by quantitative real-time polymerase chain reaction(RT-qPCR).Expressions of the inflammatory cytokines,IL-1βand IL-6 were tested by ELISA.Results CCK8 assay showed the survival rate had no significant difference between the control and treated group(P>0.05).Flow cytometry analysis showed cell cycle arrest at S phase in the IL-36β-treated groups compared with the control group(P<0.05).RT-qPCR verified the decreased mRNA expressions of keratin 10 and involucrin in the IL-36β-treated groups compared with the negative control(P<0.01).ELISA showed 100 ng/ml IL-36βenhanced levels of IL-1βand IL-6 in culture supernatants of HaCaT cells compared with the negative control(P<0.05).Conclusion Taken together,these findings suggest that IL-36βcould induce cell cycle arrest at S phase,inhibit keratin 10 and involucrin expressions and promote inflammatory activity in HaCaT cell lines.
基金supported by grants from the National Natural Science Foundation of China(No.30972654,No.81101191,No.81271765 and No.81171495)
文摘Summary： This study examined the correlation of the expression of interleukin-36 （IL-36）, a novel member of interleukin-1 （IL-1） family, with p38 mitogen-activated protein kinase （p38 MAPK） and nu clear factor-kappa B （NF-kB） pathways in psoriasis vulgaris skin lesions. The expression levels of IL-36a, IL-3613, IL-367, phosphorylated p38 MAPK, and NF-id3p65 were detected in the skin tissues of 38 psoriasis patients and 17 healthy control subjects by real-time quantitative reverse transcription po lymerase chain reaction （qRT-PCR） and Western blotting. The cytokine expression levels were com pared between the psoriasis group and the control group. A correlation analysis between cytokine pro teins was performed in the psoriasis group. Results showed that the expression levels of IL-36a, IL-3613, IL-36y, phosphorylated p38 MAPK and NF-rh3p65 in the psoriasis group were Significantly higher than those in the control group （P〈0.001）. In the psoriasis group, the IL-36 cytokine expression was positively correlated with phosphorylated p38 MAPK and NF-kBp65 expression （P〈0.05）. A significant positive correlation was also found between the phosphorylated p38 MAPK and NF-v,.Bp65 expression （P〈0.01）. It was concluded that the increased IL-36 expression is correlated with p38 MAPK and NF-kB pathways in psoriasis vulgaris skin lesions. All the three factors may be jointly involved in the pathogenesis and local inflammatory response of psoriasis.
