In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain r...In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the expression of IL-23 （p19/p40） and IL-12 （p35/p40）. The results showed that the expression of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic lesion than those of non-lesional skin and normal skin. The levels of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic non-lesional skin than normal skin. However, no significant difference was found in the level of IL-12p35 mRNA among the psoriatic lesional skin, nonesional skin and normal skin. It was suggested that IL-23 might be more important in the pathogenesis of psoriasis than IL- 12.展开更多
In order to investigate the role of Th17 cytokines in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-17, IL-23 (p19/p40), and IL-6 in sk...In order to investigate the role of Th17 cytokines in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-17, IL-23 (p19/p40), and IL-6 in skin lesions and non-lesions of the patients with psoriasis and skin tissues of normal subjects. The results showed that the mRNA expression levels of IL-17, IL-23p19, IL-23p40 and IL-6 in psoriasis leision were significantly higher than those of non-leisions (1.231±0.843 vs 1.003±0.044, 1.166±0.142 vs 0.765±0.133, 1.125±0.104 vs 0.730±0.103, 1.186±0.222 vs 0.976±0.122, respectively, all P<0.05). Meanwhile, The expression levels of IL-17 mRNA, IL-23p19 mRNA, IL-23p40 mRNA and IL-6 mRNA were higher in non-leisions than those in normal skin tissues (1.003±0.044 vs 0.620±0.104, 0.765±0.133 vs 0.584±0.078, 0.730±0.103 vs 0.000 ±0.000, 0.976±0.122 vs 0.656±0.121, respectively, all P<0.05). The overexpression of Th17 cy- tokines in the skin lesions of patients with psoriasis may indicate that Th17 cytokines play a very important role in the immunopathogenesis of psoriasis.展开更多
While there is mounting evidence that interleukin （IL）-23-IL-17 axis plays a critical role in the pathogenesis of various autoimmune diseases, much remains to be elucidated on how IL-23 is induced in the pathologica...While there is mounting evidence that interleukin （IL）-23-IL-17 axis plays a critical role in the pathogenesis of various autoimmune diseases, much remains to be elucidated on how IL-23 is induced in the pathological processes. IL-23 is a heterodimer composed of p19 and p40, the latter being shared with IL-12. We previously reported that prostaglandin （PG） E2 promotes CD40-mediated induction of 1123a （p19） expression through its E receptor subtype 4 （EP4） receptor in splenic dendritic cells （DCs）. Here, we have analyzed signaling pathways regulating 1123a induction in the cross talk between EP4 and CD40 in bone marrow-derived DCs. We found that PGE2 synergistically induced 1123a transcription with CD40 signaling. An EP4 agonist, but not agonists of EP1, EP2, or EP3, reproduced this action. Stimulation of CD40 with an agonist antibody evoked biphasic induction of 1123a expression, with the early phase peaking at 1 h and the late phase peaking at 12 h and lasting up to 36 h after stimulation, whereas induction by lipopolysaccharide or tumor necrosis factor-α was transient. The early phase induction by CD40 stimulation was absent in DCs derived from Nfkbl-deficient mice, and the late phase induction was eliminated by RNA interference of nuclear factor-kappa B （NF-κB） p100 subunit. Further, cAMP response element-binding protein （CREB） depletion completely eliminated the induction of 1123a by CD40 stimulation. The addition of the EP4 agonist amplified the induction in both phases through the cAMP-protein kinase A （PKA） pathway. These results suggest that 1123a expression in DCs is synergistically triggered by the PG E2-EP4-cAMP-PKA pathway and canonical/non-canonical NF-KB pathways and CREB activated by CD40 stimulation.展开更多
文摘In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the expression of IL-23 （p19/p40） and IL-12 （p35/p40）. The results showed that the expression of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic lesion than those of non-lesional skin and normal skin. The levels of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic non-lesional skin than normal skin. However, no significant difference was found in the level of IL-12p35 mRNA among the psoriatic lesional skin, nonesional skin and normal skin. It was suggested that IL-23 might be more important in the pathogenesis of psoriasis than IL- 12.
文摘In order to investigate the role of Th17 cytokines in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-17, IL-23 (p19/p40), and IL-6 in skin lesions and non-lesions of the patients with psoriasis and skin tissues of normal subjects. The results showed that the mRNA expression levels of IL-17, IL-23p19, IL-23p40 and IL-6 in psoriasis leision were significantly higher than those of non-leisions (1.231±0.843 vs 1.003±0.044, 1.166±0.142 vs 0.765±0.133, 1.125±0.104 vs 0.730±0.103, 1.186±0.222 vs 0.976±0.122, respectively, all P<0.05). Meanwhile, The expression levels of IL-17 mRNA, IL-23p19 mRNA, IL-23p40 mRNA and IL-6 mRNA were higher in non-leisions than those in normal skin tissues (1.003±0.044 vs 0.620±0.104, 0.765±0.133 vs 0.584±0.078, 0.730±0.103 vs 0.000 ±0.000, 0.976±0.122 vs 0.656±0.121, respectively, all P<0.05). The overexpression of Th17 cy- tokines in the skin lesions of patients with psoriasis may indicate that Th17 cytokines play a very important role in the immunopathogenesis of psoriasis.
文摘While there is mounting evidence that interleukin （IL）-23-IL-17 axis plays a critical role in the pathogenesis of various autoimmune diseases, much remains to be elucidated on how IL-23 is induced in the pathological processes. IL-23 is a heterodimer composed of p19 and p40, the latter being shared with IL-12. We previously reported that prostaglandin （PG） E2 promotes CD40-mediated induction of 1123a （p19） expression through its E receptor subtype 4 （EP4） receptor in splenic dendritic cells （DCs）. Here, we have analyzed signaling pathways regulating 1123a induction in the cross talk between EP4 and CD40 in bone marrow-derived DCs. We found that PGE2 synergistically induced 1123a transcription with CD40 signaling. An EP4 agonist, but not agonists of EP1, EP2, or EP3, reproduced this action. Stimulation of CD40 with an agonist antibody evoked biphasic induction of 1123a expression, with the early phase peaking at 1 h and the late phase peaking at 12 h and lasting up to 36 h after stimulation, whereas induction by lipopolysaccharide or tumor necrosis factor-α was transient. The early phase induction by CD40 stimulation was absent in DCs derived from Nfkbl-deficient mice, and the late phase induction was eliminated by RNA interference of nuclear factor-kappa B （NF-κB） p100 subunit. Further, cAMP response element-binding protein （CREB） depletion completely eliminated the induction of 1123a by CD40 stimulation. The addition of the EP4 agonist amplified the induction in both phases through the cAMP-protein kinase A （PKA） pathway. These results suggest that 1123a expression in DCs is synergistically triggered by the PG E2-EP4-cAMP-PKA pathway and canonical/non-canonical NF-KB pathways and CREB activated by CD40 stimulation.
