| Part I The expression of miR-146a and IL-17in the skin lesions of plaque psoriasis and their correlationsObjective To investigate the expression profile of miR-146a and IL-17mRNA, TNF-a mRNA, IFN-y mRNA and their relationship in the skin of plaque psoriasis.Methods The expression of miR-146a, IL-17mRNA, TNF-a mRNA and IFN-y mRNA between the skin lesions and non-involved skin of19patients with plaque psoriasis were analyzed by qRT-PCR. The severity of skin lesions biopsied was evaluated by PSI scoring.Results The expression of miR-146a in the lesions (2.31±0.43) was higher than non-involved skins(1.17±0.24), the difference was statistically significant(n=19P<0.01),but no significant difference of miR-146a expression can be found between the progressive phase and the stable phase(P>0.05).The expression of miR-146a was positively correlated with PSI score in skin lesions(n=19r=0.53P<0.05). The expression of IL-17mRNA in the skin lesions(3.54±0.83) was higher than non-involved skin(1.02±0.44), the difference was statistically significant (n=19P<0.01), and in the progressive phase (n=124.78±1.09) was higher than the stable phase(n=71.43±0.84), the difference was statistically significant (P<0.05).No significant difference of TNF-a mRNA and IFN-y mRNA expression can be found between skin lesions and non-involved skins of plaque psoriasis(P>0.05), nor between the progressive phase and the stable phase(P>0.05). The expression of miR-146a was positively correlated with the expression of IL-17mRNA in lesions(n=19r=0.0.68P<0.01). No correlations can be found between miR-146a and TNF-α mRNA, IFN-γ mRNA respectively(P>0.05).Conclusion Upregulation of miR-146a in the skin lesions paralled the lesion severity. The expression of miR-146a and IL-17mRNA share many similarities, indicated the possible role of miR-146a in IL-17signal pathway. Part II The expression of miR-146a and IL-17in the peripheral blood of plaque psoriasis and their correlationsObjective To investigate the expression profile of miR-146a and IL-17, TNF-a, IFN-y in the peripheral blood of plaque psoriasis and their correlations.Methods Peripheral blood of20patients with plaque psoriasis(12of them donated by biopsy patients) and10healthy controls was studied. The serum concentration of IL-17, TNF-a and IFN-y were measured by ELISA. The PBMCs were isolated by density gradient centrifugation method. qRT-PCR reaction was used to detect the relative expression of miR-146a and IL-17mRNA,TNF-a mRNA, IFN-y mRNA in their PBMCs. The severity of disease was evaluated by PASI scoring.Results The expression of miR-146a in the plaque psoriasis(n=202.60±1.02) was higher than healthy controls(n=100.42±0.07), the difference was statistically significant (P<0.05), no expression differences can be seen between the progressive phase and the stable phase (P>0.05). The expression of miR-146a was positively correlated with current duration in the progressive patients(n=10r=0.74P<0.05), correlated with PASI score (n=20r=0.67P<0.01). The serum expression of IL-17in plaque psoriasis (n=204.41±0.62pg/ml) was higher than healthy controls (n=102.49±0.18pg/ml), the difference was statistically significant(P<0.05), and the expression of IL-17in the progressive phase (n=105.67±1.09pg/ml) was higher than the stable phase (n=103.14±0.32pg/ml), the difference was statistically significant (P<0.05), IL-17miRNA of PBMCs in the progressive phase (n=101.42±0.31) was higher than stable phase(n=100.34±0.19), the difference was statistically significant(P<0.01). No significant difference of TNF-a and IFN-y serum expression can be found between plaque psoriasis and healthy controls (P>0.05), the serum expression of TNF-α expression in the stable phase (n=101.31±0.38pg/ml) was higher than the progressive phase (n=100.23±0.12pg/ml), the difference was statistically significant(P<0.05). No significant difference of TNF-α mRNA, IFN-γ, IFN-γ mRNA expression can be found between the progressive phase and the stable phase (P>0.05). The expression of miR-146a was positively correlated with IL-17level in serum(n=20r=0.78P<0.001) and IL-17mRNA in PBMCs(n=20r=0.59P<0.01). The expression of miR-146a in PBMCs (n=452.48±24.15) was higher than in lesions (n=41.89±0.99), the difference was statistically significant(P<0.05). No correlation was found between miR-146a expression in lesions and in PBMCs(P>0.05).Conclusion Upregulation of miR-146a in PBMCs is a potential clinical biomarker of severity and activity of psoriasis. The close correlation of miR-146a and IL-17expression indicated the regulation role of miR-146a to IL-17production. Part Ⅲ The expression of IRAKI in skin and PBMCs of plaque psoriasisObjective To investigate the expression pattern of IRAK1in the skin lesions and PBMCs of plaque psoriasisMethods The gene expression of IRAK1was analyzed by qRT-PCR in6paired skin samples and in PBMCs of12patients with plaque psoriasis and10healthy controls, respectively. The protein expression of IRAK1was detected by western-blot in1paired skin samples and in PBMCs of4patients with plaque psoriasis and1case heathy control.Results The expression of IRAKI mRNA in the lesions (n=62.18±0.50) was higher than non-involved skins (n=60.28±0.2), the difference was statistically significant (P<0.01), so as to the expression of IRAK1protein. The expression of IRAKI mRNA in PBMCs of plaque psoriasis (n=120.36±0.07) was lower than healthy controls(n=101.90±0.59), the difference was statistically significant (P<0.01), so as to the expression of IRAK1protein. No significant difference of IRAKI mRNA expression can be found between the progressive phase and the stable phase in skin or in PBMCs(P>0.05).Conclusion The reverse expression of target gene IRAK1indicated the differential suppressive ability of miR-146a in the lesions and PBMCs. Dampening effect of miR-146a to IRAK1in the skin lesions may contribute to the local pathogenesis of psoriasis. |
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