RESUMO
Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, IL-1 beta and tumor necrosis factor (TNF-alpha) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, IL-1 beta and TNF-alpha in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and IL-1 beta on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and IL-1 beta could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than IL-1 beta or TNF-alpha. These responses were observed in a dose- responsive manner. In addition, IL-17 or IL-1 beta neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and IL-1 beta appears to upregulate the expression of IL-23p19 in RA-SFMC.
Assuntos
Humanos , Anticorpos Neutralizantes , Artrite Reumatoide , Ensaio de Imunoadsorção Enzimática , Fibroblastos , Imuno-Histoquímica , Interleucina-17 , Interleucina-1beta , Interleucina-23 , Subunidade p19 da Interleucina-23 , Articulações , Osteoartrite , RNA Mensageiro , DNA Polimerase Dirigida por RNA , Líquido Sinovial , Membrana Sinovial , Fator de Necrose Tumoral alfaRESUMO
Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, IL-1 beta and tumor necrosis factor (TNF-alpha) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, IL-1 beta and TNF-alpha in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and IL-1 beta on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and IL-1 beta could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than IL-1 beta or TNF-alpha. These responses were observed in a dose- responsive manner. In addition, IL-17 or IL-1 beta neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and IL-1 beta appears to upregulate the expression of IL-23p19 in RA-SFMC.
Assuntos
Humanos , Anticorpos Neutralizantes , Artrite Reumatoide , Ensaio de Imunoadsorção Enzimática , Fibroblastos , Imuno-Histoquímica , Interleucina-17 , Interleucina-1beta , Interleucina-23 , Subunidade p19 da Interleucina-23 , Articulações , Osteoartrite , RNA Mensageiro , DNA Polimerase Dirigida por RNA , Líquido Sinovial , Membrana Sinovial , Fator de Necrose Tumoral alfaRESUMO
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 cytokines in the skin lesions of patients with psoriasis may indicate that Th17 cytokines play a very important role in the immunopathogenesis of psoriasis.
RESUMO
In order to investigate the mRNA expression and function of interleukin-23 (p19/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, non-lesional skin and normal skin. It was suggested that IL-23 might be more important in the pathogenesis of psoriasis than IL-12.