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1.
Korean J Intern Med ; 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32550719

RESUMO

Background/Aims: The present study aimed to investigate whether tocotrienol regulates interleukin 17 (IL-17)-induced osteoclastogenesis in rheumatoid arthritis (RA). Methods: We evaluated the effect of tocotrienol on IL-17-induced receptor activator of nuclear factor kappa B ligand (RANKL) production using RA fibroblast-like synoviocyte (FLS), together with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Osteoclast differentiation was confirmed after culturing IL-17-treated RA FLS and Th17 cells with tocotrienol and monocytes. We analyzed the suppressive effect of tocotrienol on Th17 cells percentage or Th17-cytokine levels among peripheral blood mononuclear cells using flow cytometry. Results: We found that IL-17 stimulated FLS to produce RANKL and tocotrienol decreased this IL-17-induced RANKL production. Tocotrienol decreased the IL-17-induced activation of mammalian target of rapamycin, extracellular signal-regulated kinase, and inhibitor of kappa B-alpha. When monocytes were incubated with IL-17, RANKL, IL-17-treated FLS or Th17 cells, osteoclasts were differentiated and tocotrienol decreased this osteoclast differentiation. Tocotrienol reduced Th17 cell differentiation and the production of IL-17 and sRANKL; however, tocotrienol did not affect Treg cell differentiation. Conclusions: Tocotrienol inhibited IL-17- activated RANKL production in RA FLS and IL-17-activated osteoclast formation. In addition, tocotrienol reduced Th17 differentiation. Therefore, tocotrienol could be a new therapeutic choice to treat bone destructive processes in RA.

3.
Gut Liver ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32307975

RESUMO

Background/Aims: Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT. Methods: Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR). Results: Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030). Conclusions: HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR.

4.
Int J Med Sci ; 17(6): 815-823, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32218703

RESUMO

Importin-11 (Ipo11) is a novel member of the human importin family of transport receptors (karyopherins), which are known to mediate the nucleocytoplasmic transport of protein and RNA cargos. Despite its role in the transport of protein, we found that knockout of Ipo11 nuclear import factor affects normal embryonic development and govern embryo-lethal phenotypes in mice. In this study, we for the first time produced a mouse line containing null mutation in Ipo11 gene utilized by gene trapping. The Ipo11-/- embryos showed an embryonic lethal phenotype. The Ipo11-/- embryos showed a reduced size at embryonic day 10.5 (E10.5) when compared with Ipo11+/+ or Ipo11+/- embryos and died by E11.5. Whereas Ipo11+/- mice were healthy and fertile, and there was no detectable changes in embryonic lethality and phenotype when reviewed. In the X-gal staining with the Ipo11-/- or Ipo11+/- embryos, strong X-gal staining positivity was detected systematically in the whole mount embryos at E10.5, although almost no X-gal positivity was detected at E9.5, indicating that the embryos die soon after the process of Ipo11 expression started. These results indicate that Ipo11 is essential for the normal embryonic development in mice.

6.
Korean J Intern Med ; 35(1): 12-24, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31722515

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthritis, and the complex interaction and activation of innate and adaptive immune cells are involved in RA pathogenesis. Mast cells (MCs) are one of the tissue-resident innate immune cells, and they contribute to RA pathogenesis. In the present review, the evidence of the pathologic role of MC in RA is discussed based on human and animal data. In addition, the potential role of MC in RA pathogenesis and the research area that should be focused on in the future are suggested.

7.
Int J Med Sci ; 16(12): 1557-1563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839743

RESUMO

E2F3, a member of the E2F family, plays a critical role in cell cycle and proliferation by targeting downstream, retinoblastoma (RB) a tumor suppressor family protein. The purpose of this study, was to investigate the role and function of E2F3 in vivo. We examined phenotypic abnormalities, by deletion of the E2f3 gene in mice. Complete ablation of the E2F3 was fully penetrant, in the pure C57BL/6N background. The E2f3+/ - mouse embryo developed normally without fatal disorder. However, they exhibited reduced body weight, growth retardation, skeletal imperfection, and poor grip strength ability. Findings suggest that E2F3 has a pivotal role in muscle and bone development, and affect normal mouse growth.


Assuntos
Desenvolvimento Ósseo/genética , Fator de Transcrição E2F3/genética , Desenvolvimento Embrionário/genética , Músculo Esquelético/crescimento & desenvolvimento , Animais , Apoptose/genética , Peso Corporal/genética , Ciclo Celular/genética , Proliferação de Células/genética , Embrião de Mamíferos , Humanos , Camundongos , Camundongos Knockout , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Fenótipo
8.
Arthritis Res Ther ; 21(1): 283, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831038

RESUMO

BACKGROUND: The inflammatory cascade in the rheumatoid arthritis (RA) synovium is modulated by a variety of cytokine and chemokine networks; however, the roles of IL-26, in RA pathogenesis, are poorly defined. Here, we investigated the functional role of interleukin-26 (IL)-26 in osteoclastogenesis in RA. METHODS: We analyzed levels of IL-20 receptor subunit A (IL-20RA), CD55, and receptor activator of nuclear factor kappaB (NF-κB) ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs) using confocal microscopy. Recombinant human IL-26-induced RANKL expression in RA-FLSs was examined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor (M-CSF) and IL-26, after which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells. Additionally, osteoclastogenesis was evaluated by monocytes co-cultured with IL-26-prestimulated FLSs. RESULTS: The expression of IL-20RA in RA-FLSs was higher than that in osteoarthritis-FLSs. Additionally, in IL-26-pretreated RA-FLSs, the expression of IL-20RA (but not IL-10 receptor subunit B) and RANKL increased in a dose-dependent manner, with IL-26-induced RANKL expression reduced by IL-20RA knockdown. Moreover, IL-26-induced RANKL expression was significantly downregulated by inhibition of signal transducer and activator of transcription 1, mitogen-activated protein kinase, and NF-κB signaling. Furthermore, IL-26 promoted osteoclast differentiation from peripheral blood monocytes in the presence of low dose of RANKL, with IL-26 exerting an additive effect. Furthermore, co-culture of IL-26-pretreated RA-FLSs with peripheral blood monocytes also increased osteoclast differentiation in the absence of addition of RANKL. CONCLUSIONS: IL-26 regulated osteoclastogenesis in RA through increased RANKL expression in FLSs and direct stimulation of osteoclast differentiation. These results suggest the IL-26/IL-20RA/RANKL axis as a potential therapeutic target for addressing RA-related joint damage.

9.
Immune Netw ; 19(4): e27, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31501715

RESUMO

The purpose of this study was to determine the regulatory role of intravenous Ig (IVIg) in Th17 cytokine-induced RANK ligand (RANKL) expression and osteoclast (OC) differentiation from OC precursors (pre-OC). Human CD14+ monocytes were isolated and stimulated by Th17 cytokines (IL-17, IL-21, and IL-22) and RANKL expression was investigated using a real-time PCR. CD14+ monocytes were incubated with RANKL, Th17 cytokines, and M-CSF, with/without IVIg, and OC differentiation was determined by counting tartrate-resistant acid phosphatase-positive multinucleated cells. OC differentiation was investigated after monocytes were cocultured with Th17 cells in the presence of IVIg. Th17 cell differentiation was determined using enzyme-linked immunosorbent assay and flow cytometry after CD4+ T cells were cultured with IVIg under Th17 condition. Th17 cytokines stimulated monocytes to express RANKL and IVIg suppressed the Th17 cytokine-induced RANKL expression. OCs were differentiated when pre-OC were cocultured with RANKL or Th17 cytokines and IVIg reduced the osteoclastogenesis. IVIg also decreased osteoclastogenesis when pre-OC were cocultured with Th17 cells. IVIg decreased both Th17 and Th1 cell differentiation while it did not affect Treg cell differentiation. In summary, IVIg inhibited Th17 cytokine-induced RANKL expression and OC differentiation. IVIg reduced osteoclastogenesis when monocytes were cocultured with Th17 cells. IVIg also reduced Th17 polarization. IVIg could be a new therapeutic option for Th17 cell-mediated osteoclastogenesis.

11.
J Clin Med ; 8(7)2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295961

RESUMO

This study aimed to investigate the regulatory effect of SKI305X, a mixed extract of three herbs, in T helper (Th)17 cytokine-induced inflammation and joint destruction in rheumatoid arthritis (RA). Synovial fibroblasts were isolated from RA patients and cultured with Th17 cytokines including interleukin (IL)-17, IL-21, and IL-22 and SKI306X, and tumor necrosis factor (TNF)-, IL-1, and receptor activator of nuclear factor kappa-Β ligand (RANKL) expression and production were investigated using real-time PCR and ELISA of culture media. After peripheral blood (PB) cluster of differentiation (CD)14+ monocytes were cultured in media supplemented with Th17 cytokines and SKI306X, tartrate-resistant acid phosphatase positive (TRAP+) multinucleated giant cells (mature osteoclasts) were enumerated and gene expression associated with osteoclast maturation was assessed via real-time PCR analysis. After PB monocytes were co-cultured with IL-17-stimulated RA synovial fibroblasts in the presence of SKI306, osteoclast differentiation was assessed. When RA synovial fibroblasts were cultured with IL-17, IL-21, and IL-22, TNF-, IL-1, and RANKL expression and production were increased; however, SKI306X reduced cytokine expression and production. When PB monocytes were cultured in media supplemented with Th17 cytokines, osteoclast differentiation was stimulated; however, SKI306X decreased osteoclast differentiation and osteoclast maker expression. When PB monocytes were co-cultured with IL-17-stimulated RA synovial fibroblasts, osteoclast differentiation was increased; however, SKI306X decreased osteoclast differentiation and osteoclast maker expression. SKI306X reduced Th17 cytokine-induced TNF-, IL-1, and RANKL expression and osteoclast differentiation, providing novel insights into adjuvant therapy for regulating inflammation and joint destruction in RA.

12.
J Biochem ; 166(3): 259-270, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31086948

RESUMO

This study aimed to determine the regulatory role of toll-like receptor 7 (TLR7) in receptor activator of nuclear factor kappa-B ligand (RANKL) production and osteoclast differentiation in rheumatoid arthritis (RA). In confocal microscopy, the co-expression of TLR7, CD55 and RANKL was determined in RA synovial fibroblasts. After RA synovial fibroblasts were treated with imiquimod, the RANKL gene expression and protein production were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis from peripheral blood CD14+ monocytes which were cultured with imiquimod was assessed by determining the numbers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. The signal pathways mediating the TLR7-induced RANKL expression and osteoclastogenesis were analysed after inhibition of intracellular signal molecules and their phosphorylation. Imiquimod stimulated the expression of TLR7 and RANKL and production of RANKL in RA synovial fibroblasts, increasing the phosphorylation of TRAF6, IRF7, mitogen-activated protein kinases (MAPK), c-Jun and NFATc1. When CD14+ monocytes were cultured with imiquimod or co-cultured with imiquimod-pre-treated RA synovial fibroblasts, they were differentiated into TRAP+ multinucleated osteoclasts in the absence of RANKL. TLR7 activation-induced osteoclastogenesis in RA through direct induction of osteoclast differentiation from its precursors and up-regulation of RANKL production in RA synovial fibroblasts. Thus, the blockage of TLR7 pathway could be a promising therapeutic strategy for preventing bone destruction in RA.


Assuntos
Artrite Reumatoide/metabolismo , Fibroblastos/metabolismo , Osteogênese , Receptor 7 Toll-Like/metabolismo , Idoso , Artrite Reumatoide/patologia , Células Cultivadas , Feminino , Fibroblastos/patologia , Humanos , Masculino , Pessoa de Meia-Idade
13.
Korean J Intern Med ; 34(6): 1197-1209, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31014065

RESUMO

Immune checkpoint inhibitors (ICIs) have revolutionized anticancer therapy due to their long-term clinical benefits and immune boosting mechanisms. However, despite their consistent therapeutic effects, the use of ICIs is associated with a spectrum of adverse events due to their autoimmune and auto-inflammatory actions. These adverse events can affect any organ system, including the endocrine, neurologic, gastrointestinal, cardiac, skin, pulmonary, and musculoskeletal systems. Of the immune-related adverse events (irAEs), rheumatic complications are common and appear to be distinct from irAEs in other organs in terms of variability of onset time, capacity for persistence, and relationship with pre-existing autoimmune rheumatologic diseases. In this article, we review the mechanisms of the anti-cancer effects of ICIs, the irAEs of immuno-oncology drugs, and the general recommendations for managing irAEs. In particular, we focus on rheumatologic irAEs and discuss their prevalence, clinical characteristics, and management.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Neoplasias/tratamento farmacológico , Doenças Reumáticas/induzido quimicamente , Humanos , Neoplasias/imunologia , Prevalência , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/imunologia , Doenças Reumáticas/terapia , Fatores de Risco , Resultado do Tratamento , Evasão Tumoral , Microambiente Tumoral
15.
J Med Food ; 22(2): 152-161, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30596535

RESUMO

We investigated the immune-regulatory function of quercetin, in interleukin (IL)-17-produced osteoclastogenesis in rheumatoid arthritis (RA). RA fibroblasts-like synoviocytes (RA-FLS) were stimulated with IL-17, and the mRNA expression and secretion of receptor activator of nuclear factor kappa-B ligand (RANKL) were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. CD14+ monocytes (osteoclast precursors) were stimulated with IL-17, RANKL, with/without quercetin, and tartrate-resistant acid phosphatase activity was evaluated to assess osteoclast differentiation. Osteoclast differentiation was investigated after coculturing IL-17-stimulated RA-FLS and Th17 cells with monocytes. CD4+ T cells were cocultured with quercetin under Th17-inducing conditions, and their differentiation to Th17 cells and Treg cells was determined by flow cytometry analysis. We found that IL-17 stimulated RA-FLS to produce RANKL and quercetin decreased the IL-17-induced RANKL protein levels. Quercetin decreased the IL-17-produced activation of mammalian target of rapamycin, extracellular signal-regulated kinase and inhibitor of kappa B-alpha. When monocytes were stimulated with IL-17, macrophage colony-stimulating factor or RANKL, mature osteoclasts were formed, and quercetin decreased this osteoclastogenesis. When monocytes were cultured with IL-17-prestimulated RA-FLS or Th17 cells, osteoclasts were produced, and quercetin decreased this osteoclast differentiation. In Th17-differentiation conditions, quercetin suppressed Th17 cell and the production of IL-17, but quercetin did not affect Treg cells. Quercetin inhibits IL-17-stimulated RANKL production in RA-FLS and IL-17-stimulated osteoclast formation. Quercetin reduces Th17 differentiation. Quercetin could be an additional therapeutic option for bone destructive processes in RA.


Assuntos
Artrite Reumatoide , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Quercetina/farmacologia , Fosfatase Ácida/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Diferenciação Celular , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Interleucina-17/efeitos adversos , Interleucina-17/metabolismo , Monócitos , Extratos Vegetais/uso terapêutico , Quercetina/uso terapêutico , Ligante RANK/metabolismo , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fosfatase Ácida Resistente a Tartarato/metabolismo , Células Th17
16.
Clin Oral Investig ; 23(3): 1415-1423, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30032469

RESUMO

OBJECTIVES: The aim of this study was to investigate the diagnostic accuracy of rheumatoid factor (RF) isotype for the detection of primary Sjogren's syndrome (pSS) and evaluate the clinical and serological associations of immunoglobulin (Ig) A RF in patients with pSS. MATERIALS AND METHODS: RF levels were measured in 77 and 37 patients with pSS and idiopathic sicca symptoms, respectively, using ELISA and analysed with respect to clinical and laboratory disease characteristics. Receiver operating characteristic curves were used to determine and compare the diagnostic accuracy of IgA RF with other diagnostic tests. RESULTS: Serum levels of IgA RF were significantly higher in patients with pSS than in those with idiopathic sicca symptoms. IgA RF showed sensitivity, specificity, positive, and negative predictive values of 83.1, 78.4, 88.9, and 69.0%, respectively, for pSS diagnosis. IgA RF was associated with xerostomia, severe sialoscintigraphic grade, low unstimulated salivary flow rate (USFR), antinuclear antibody, high IgG and IgM/G RF levels, and low C3 levels in patients with pSS. IgA RF titres had positive correlations with sialoscintigraphic grade and IgG and IgG/M RF levels and had negative correlations with USFR and C3 levels. CONCLUSION: Our findings confirmed the potential of IgA RF to distinguish pSS from idiopathic sicca symptoms. The presence of IgA RF in patients with pSS was associated with significantly worse exocrine function and active serologic profile. No association between IgA RF and extra-glandular manifestations was noted. CLINICAL RELEVANCE: IgA RF should be the predictive and diagnostic marker in patients with pSS.


Assuntos
Imunoglobulina A/sangue , Fator Reumatoide/sangue , Síndrome de Sjogren/diagnóstico , Idoso , Anticorpos Antinucleares/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Síndrome de Sjogren/sangue
17.
Korean J Intern Med ; 34(3): 651-659, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29166759

RESUMO

BACKGROUND/AIMS: Magnetic resonance imaging (MRI) is a sensitive and useful method for the detection of synovitis and joint destruction in rheumatoid arthritis (RA) patients. However, the patterns of MRI-detected bone erosion, bone marrow edema (BME), synovitis, and tenosynovitis have received insufficient attention. Therefore, this study evaluated the patterns of bone erosion, BME, synovitis, and tenosynovitis, and calculated the RA-MRI score (RAMRIS) of patients with RA at the carpal and metacarpophalangeal (MCP) joints using MRI. METHODS: MRI datasets from 43 RA patients were analyzed. All patients had undergone MRI of one wrist. In addition, 36 patients had MCP joint images taken, and three had also received MRI of the contralateral wrist and MCP joints. The MR images were evaluated for bone erosion, BME, and synovitis in consensus by two blinded readers according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RAMRIS. The MRI-detected tenosynovitis was evaluated based on Haavardsholm's tenosynovitis score. RESULTS: The capitate, lunate, triquetrum, and hamate bones were the most common sites of erosion and BME and showed the highest RAMRIS erosion and BME scores. Moreover, MRI-detected tenosynovitis was present in 78.3% of all patients with RA, and the extensor compartment 4 and flexor digitorum profundus and superficialis were frequently affected. CONCLUSION: This study identified the distribution and prevalence of MRI-detected bone erosion, BME, synovitis, and tenosynovitis of the wrist and MCP joints in RA patients. The patterns of the MRI-detected abnormalities may help to select sites for the application of MRI protocols in clinical trials and practice.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Imagem por Ressonância Magnética , Articulação Metacarpofalângica/diagnóstico por imagem , Articulação do Punho/diagnóstico por imagem , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Medula Óssea/diagnóstico por imagem , Edema/diagnóstico por imagem , Edema/epidemiologia , Edema/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Sinovite/diagnóstico por imagem , Sinovite/epidemiologia , Sinovite/etiologia , Tenossinovite/diagnóstico por imagem , Tenossinovite/epidemiologia , Tenossinovite/etiologia
18.
Korean J Intern Med ; 34(1): 210-219, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-28286938

RESUMO

BACKGROUND/AIMS: This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). METHODS: After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes. After human peripheral CD4+ T cells were cultured with NAC under Th17 condition, IL-17, interferon γ, IL-4, Foxp3, RANKL, and IL-2 expression and production was determined by flow cytometry or ELISA. RESULTS: When RA synovial fibroblasts were stimulated by IL-17, IL-17 stimulated the production of RANKL, and NAC reduced the IL-17-induced RANKL production in a dose-dependent manner. NAC decreased IL-17-activated phosphorylation of mammalian target of rapamycin, c-Jun N-terminal kinase, and inhibitor of κB. When human peripheral blood CD14+ monocytes were cultured with macrophage colony-stimulating factor and IL-17 or RANKL, osteoclasts were differentiated, and NAC reduced the osteoclastogenesis. After human peripheral CD4+ T cells were co-cultured with IL-17-pretreated RA synovial fibroblasts or Th17 cells, NAC reduced their osteoclastogenesis. Under Th17 polarizing condition, NAC decreased Th17 cell differentiation and IL-17 and RANKL production. CONCLUSION: NAC inhibits the IL-17-induced RANKL production in RA synovial fibroblasts and IL-17-induced osteoclast differentiation. NAC also reduced Th17 polarization. NAC could be a supplementary therapeutic option for inflammatory and bony destructive processes in RA.


Assuntos
Acetilcisteína/farmacologia , Artrite Reumatoide/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Ligante RANK/metabolismo , Células Th17/efeitos dos fármacos , Adulto , Idoso , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/imunologia , Fibroblastos/patologia , Humanos , Técnicas In Vitro , Interleucina-17/metabolismo , Pessoa de Meia-Idade , Osteogênese/imunologia , Ligante RANK/genética , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Células Th17/imunologia , Células Th17/patologia
19.
Korean J Intern Med ; 34(6): 1372-1380, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29722248

RESUMO

BACKGROUND/AIMS: To define standard reference values for musculoskeletal ultrasonography (MSUS) in Korea. METHODS: A total of 251 healthy adults were recruited for this study. Ultrasonography was performed by experienced rheumatologists who had undergone four appropriate training programs in Korea. A General Electric LOGIQ electronic ultrasound device fitted with a 12 MHz linear transducer was employed. Mean values ± standard deviations (SDs) were defined as standard reference values. Intraclass correlation coefficients was employed to evaluate the extent of inter- and intraobserver agreement when MSUS measurements were made. RESULTS: The 251 study participants included 122 males. Mean subject age was 28.6 years. The average bone-to-capsule distance of the right-side second and third metacarpophalangeal (MCP) joints were 0.68 and 0.72 mm respectively, and those of the left-side joints 0.62 and 0.68 mm. The cartilage thicknesses of the rightside second and third MCP joints were 0.55 and 0.55 mm, and those of the leftside joints were 0.55 and 0.56 mm, respectively. The bone-to-capsule distances of the right and left wrists were 0.80 and 0.82 mm. In 12.4% of participants (31/251), the erosion score of the humeral head was 1.71. In the right-side knee joint, mean cartilage thicknesses of the medial and lateral condyles were 1.86 and 2.03 mm in longitudinal scans. High overall interobserver agreement was evident after appropriate training that included instruction on standard MSUS methodology. CONCLUSION: We defined standard reference values for MSUS in healthy Korean adults. The reliabilities of interobserver agreements were high after appropriate training program.


Assuntos
Sistema Musculoesquelético/diagnóstico por imagem , Ultrassonografia/normas , Adulto , Pontos de Referência Anatômicos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Valores de Referência , Reprodutibilidade dos Testes , República da Coreia , Adulto Jovem
20.
Clin Exp Rheumatol ; 37(2): 270-278, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30148447

RESUMO

OBJECTIVES: Macrophage migration inhibitory factor (MIF) is a proinflammatory, chemotactic, and tissue destructive cytokine. This study determined monosodium urate crystal-induced MIF production and its interaction with interleukin (IL)-8 in gout. METHODS: Peripheral blood (PB), synovial fluid (SF), and clinical data were obtained from 98 patients with gout. SF and serum concentrations of MIF and IL-8 were measured using ELISA. SF monocytes and neutrophils were cultured with monosodium urate (MSU) crystals and the cytokine production was determined. The signalling pathways involved were determined using signal inhibitors. The interaction between MIF and IL-8 was investigated. RESULTS: SF MIF was higher in acute gout and that in serum was higher in patients with intercritical gout compared with controls. SF MIF was positively correlated with SF leukocyte and neutrophil counts and IL-8. The expression of MIF was similar in SF neutrophils and monocytes, while IL-8 was higher in monocytes. MSU crystals induced MIF production in monocytes and IL-8 production in neutrophils. This effect was decreased by inhibiting Fc-gamma receptor 1 and toll-like receptor 4. IL-8 increased MIF production in monocytes while MIF increased interleukin-8 production in neutrophils. CONCLUSIONS: MIF and IL-8 are highly produced in acute gout. MSU crystals induced MIF production in monocytes and IL-8 production in neutrophils with a reciprocal interaction between the two cytokines.


Assuntos
Gota , Interleucina-8/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Gota/metabolismo , Humanos , Neutrófilos , Ácido Úrico
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