Aim To investigate the effects of JAK inhibitor （SHR0302） on adjuvant-induced arthritis （AA） rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 pathway, including Thl7, Treg, tot...Aim To investigate the effects of JAK inhibitor （SHR0302） on adjuvant-induced arthritis （AA） rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 pathway, including Thl7, Treg, total B cells and memory B cells. Methods Animals were divided randomly into 6 groups including normal control, AA, SHR0302 （0.3, 1.0, 3.0 nag · kg^-1, ig） and MTX （0.5 nag · kg^-1 , ig） . The effects of SHR0302 on AA rats by evaluating arthritis index, arthritis global assessment and paw swelling degree, histopathology of joint and spleen, inflammatory cytokine and antibody production in serum. We examined the proliferation of T, B and FLS by CCK8 kit; Thl7, Treg, total B and memory B cell proportion was measured by flow cytometry; Cytokines TNF-αβ, IL-1β, IL-10, IL-17 and antibody IgG1, IgG2a levels in serum were measured by ELISA kits; The ex- pression of p-JAK1 and p-STAT3 was measured by Western blot analysis. Results SHR0302 suppressed the se- verity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and allevia- ted histopathology of spleen and joint of AA rats. SHR0302 can inhibit the proliferation of T, B and FLS, and down-regulated cytokines TNF-α, IL-1β, IL-17 and antibody IgG1, IgG2a levels, and suppressed the proportion of Thl7 and total B, and inhibited JAK1-STAT3 phosphorylation; There was no significant effect on Treg function and memory B cell proportion. Conclusion SHR0302 may attenuate the severity of AA rats, partially through signifi- cantly reducing Thl7 function and total B cell proportion by inhibiting JAK1-STAT3 phosphorylation.展开更多
目的:检测慢性鼻窦炎伴鼻息肉患者外周血中Th9、Th17及Treg细胞的表达水平,初步探讨3种细胞对鼻息肉形成的影响。方法:收集46例慢性鼻窦炎伴鼻息肉患者的外周静脉血为鼻息肉组,另收集22例单纯鼻出血或鼻中隔偏曲患者外周静脉血作为对照...目的:检测慢性鼻窦炎伴鼻息肉患者外周血中Th9、Th17及Treg细胞的表达水平,初步探讨3种细胞对鼻息肉形成的影响。方法:收集46例慢性鼻窦炎伴鼻息肉患者的外周静脉血为鼻息肉组,另收集22例单纯鼻出血或鼻中隔偏曲患者外周静脉血作为对照组。1采用流式细胞术检测鼻息肉组和对照组患者外周静脉血中Th9、Th17及Treg细胞的表达率。2用SYBR Green I实时荧光定量PCR检测两组患者外周静脉血中Th9,Th17及Treg细胞相关转录因子IL-9mRNA,PU.1,IRF-4,RoRc及Foxp3的表达水平。3采用SPSS16.0统计软件,分析三种细胞及相关转录因子在鼻息肉组与对照组外周血中的差异性,并对鼻息肉组Th9与Th17及Th17与Treg之间的相关性进行分析。结果:1鼻息肉组外周静脉血中Th9、Th17细胞的表达率(1.29%±0.18%,4.03%±0.69%)明显高于对照组(0.45%±0.14%,1.35%±0.26%),而外周静脉血中的Treg细胞的表达率(2.98%±0.13%)明显低于对照组(5.44%±0.57%),差异均有统计学意义(P<0.05)。2鼻息肉组的转录因子IL-9mRNA,PU.1,IRF-4,RoRc的相对表达量明显高于对照组,而Foxp3的相对表达量低于对照组,差异均有统计学意义(P<0.05)。3鼻息肉患者外周静脉血中Th9与Th17细胞之间无明显相关性(P>0.05),Th17与Treg细胞之间呈负相关(r=-0.549,P<0.05)。结论:外周静脉血中高水平的Th9和Th17细胞对鼻息肉的形成有一定促进作用,而Treg细胞的较低表达可能进一步加剧鼻息肉的发生,且在鼻息肉的发病机制中存在Th17/Treg失衡,Th17/Treg细胞平衡在鼻息肉的发病机制中起着重要的免疫调节作用。展开更多
文摘Aim To investigate the effects of JAK inhibitor （SHR0302） on adjuvant-induced arthritis （AA） rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 pathway, including Thl7, Treg, total B cells and memory B cells. Methods Animals were divided randomly into 6 groups including normal control, AA, SHR0302 （0.3, 1.0, 3.0 nag · kg^-1, ig） and MTX （0.5 nag · kg^-1 , ig） . The effects of SHR0302 on AA rats by evaluating arthritis index, arthritis global assessment and paw swelling degree, histopathology of joint and spleen, inflammatory cytokine and antibody production in serum. We examined the proliferation of T, B and FLS by CCK8 kit; Thl7, Treg, total B and memory B cell proportion was measured by flow cytometry; Cytokines TNF-αβ, IL-1β, IL-10, IL-17 and antibody IgG1, IgG2a levels in serum were measured by ELISA kits; The ex- pression of p-JAK1 and p-STAT3 was measured by Western blot analysis. Results SHR0302 suppressed the se- verity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and allevia- ted histopathology of spleen and joint of AA rats. SHR0302 can inhibit the proliferation of T, B and FLS, and down-regulated cytokines TNF-α, IL-1β, IL-17 and antibody IgG1, IgG2a levels, and suppressed the proportion of Thl7 and total B, and inhibited JAK1-STAT3 phosphorylation; There was no significant effect on Treg function and memory B cell proportion. Conclusion SHR0302 may attenuate the severity of AA rats, partially through signifi- cantly reducing Thl7 function and total B cell proportion by inhibiting JAK1-STAT3 phosphorylation.
文摘目的:检测慢性鼻窦炎伴鼻息肉患者外周血中Th9、Th17及Treg细胞的表达水平,初步探讨3种细胞对鼻息肉形成的影响。方法:收集46例慢性鼻窦炎伴鼻息肉患者的外周静脉血为鼻息肉组,另收集22例单纯鼻出血或鼻中隔偏曲患者外周静脉血作为对照组。1采用流式细胞术检测鼻息肉组和对照组患者外周静脉血中Th9、Th17及Treg细胞的表达率。2用SYBR Green I实时荧光定量PCR检测两组患者外周静脉血中Th9,Th17及Treg细胞相关转录因子IL-9mRNA,PU.1,IRF-4,RoRc及Foxp3的表达水平。3采用SPSS16.0统计软件,分析三种细胞及相关转录因子在鼻息肉组与对照组外周血中的差异性,并对鼻息肉组Th9与Th17及Th17与Treg之间的相关性进行分析。结果:1鼻息肉组外周静脉血中Th9、Th17细胞的表达率(1.29%±0.18%,4.03%±0.69%)明显高于对照组(0.45%±0.14%,1.35%±0.26%),而外周静脉血中的Treg细胞的表达率(2.98%±0.13%)明显低于对照组(5.44%±0.57%),差异均有统计学意义(P<0.05)。2鼻息肉组的转录因子IL-9mRNA,PU.1,IRF-4,RoRc的相对表达量明显高于对照组,而Foxp3的相对表达量低于对照组,差异均有统计学意义(P<0.05)。3鼻息肉患者外周静脉血中Th9与Th17细胞之间无明显相关性(P>0.05),Th17与Treg细胞之间呈负相关(r=-0.549,P<0.05)。结论:外周静脉血中高水平的Th9和Th17细胞对鼻息肉的形成有一定促进作用,而Treg细胞的较低表达可能进一步加剧鼻息肉的发生,且在鼻息肉的发病机制中存在Th17/Treg失衡,Th17/Treg细胞平衡在鼻息肉的发病机制中起着重要的免疫调节作用。
