共查询到20条相似文献,搜索用时 15 毫秒
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ukasz Kopiasz Katarzyna Dziendzikowska Joanna Gromadzka-Ostrowska 《International journal of molecular sciences》2022,23(3)
Crohn’s disease (CD), a condition characterized by chronic inflammation of the gastrointestinal tract with alternating periods of exacerbation and remission, is becoming common around the world. This study aimed to analyze the molecular mechanisms underlying the anti-inflammatory properties of oat beta-glucans of varying molar masses by modulating the expression of chemokines and their receptors as well as other proteins related to both stages of TNBS (2,4,6-trinitrobenzosulfonic acid)-induced colitis, which is an animal model of CD. The experiment involved 96 Sprague–Dawley rats, which were divided into two main groups: control and TNBS-induced colitis. Both groups of rats were further divided into three dietary subgroups, which were fed with standard feed or feed supplemented with low- or high-molar-mass oat beta-glucans for 3 (reflecting acute inflammation) or 7 days (reflecting pre-remission). The gene expression of chemokines and their receptors in the colon wall was determined by RT-PCR, and the expression of selected proteins in the mucosa was determined by immunohistochemical analysis. The results showed that acute and pre-remission stages of colitis were characterized by the increased gene expression of seven chemokines and four chemokine receptors in the colon wall as well as disrupted protein expression of CXCL1, CCL5, CXCR2, CCR5, and OPN in the mucosa. The consumption of oat beta-glucans resulted in decreased expression of most of these genes and modulated the expression of all proteins, with a stronger effect observed with the use of high-molar-mass beta-glucan. To summarize, dietary oat beta-glucans, particularly those of high molar mass, can reduce colitis by modulating the expression of chemokines and their receptors and certain proteins associated with CD. 相似文献
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Raffaella Giancola Francesco Oliva Marialucia Gallorini Noemi Michetti Clarissa Gissi Fadl Moussa Cristina Antonetti Lamorgese Passeri Alessia Colosimo Anna Concetta Berardi 《International journal of molecular sciences》2022,23(23)
Rotator cuff tendon (RCT) disease results from multifactorial mechanisms, in which inflammation plays a key role. Pro-inflammatory cytokines and tendon stem cell/progenitor cells (TSPCs) have been shown to participate in the inflammatory response. However, the underlying molecular mechanism is still not clear. In this study, flow cytometry analyses of different subpopulations of RCT-derived TSPCs demonstrate that after three days of administration, TNFα alone or in combination with IFNγ significantly decreases the percentage of CD146+CD49d+ and CD146+CD49f+ but not CD146+CD109+ TSPCs populations. In parallel, the same pro-inflammatory cytokines upregulate the expression of CD200 in the CD146+ TSPCs population. Additionally, the TNFα/IFNγ combination modulates the protein expression of STAT1, STAT3, and MMP9, but not fibromodulin. At the gene level, IRF1, CAAT (CAAT/EBPbeta), and DOK2 but not NF-κb, TGRF2 (TGFBR2), and RAS-GAP are modulated. In conclusion, although our study has several important limitations, the results highlight a new potential role of CD200 in regulating inflammation during tendon injuries. In addition, the genes analyzed here might be new potential players in the inflammatory response of TSPCs. 相似文献
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Ross M. Maltz Pedro Marte-Ortiz Therese A. Rajasekera Brett R. Loman Tamar L. Gur Michael T. Bailey 《International journal of molecular sciences》2022,23(4)
Stressor exposure increases colonic inflammation. Because inflammation leads to anxiety-like behavior, we tested whether stressor exposure in mice recovering from dextran-sulfate-sodium (DSS)-induced colitis enhances anxiety-like behavior. Mice received 2% DSS for five consecutive days prior to being exposed to a social-disruption (SDR) stressor (or being left undisturbed). After stressor exposure, their behavior was tested and colitis was assessed via histopathology and via inflammatory-cytokine measurement in the serum and colon. Cytokine and chemokine mRNA levels in the colon, mesenteric lymph nodes (MLNs), hippocampus, and amygdala were measured with RT-PCR. SDR increased anxiety-like behaviors, which correlated with serum and hippocampal IL-17A. The stressor also reduced IL-1β, CCL2, and iNOS in the colonic tissue, but increased iNOS, IFNγ, IL-17A, and TNFα in the MLNs. A network analysis indicated that reductions in colonic iNOS were related to elevated MLN iNOS and IFNγ. These inflammatory markers were related to serum and hippocampal IL-17A and associated with anxiety-like behavior. Our data suggest that iNOS may protect against extra-colonic inflammation, and when suppressed during stress it is associated with elevated MLN IFNγ, which may coordinate gut-to-brain inflammation. Our data point to hippocampal IL-17A as a key correlate of anxiety-like behavior. 相似文献
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Zi-Yu Chang Hsuan-Miao Liu Yann-Lii Leu Chung-Hua Hsu Tzung-Yan Lee 《International journal of molecular sciences》2022,23(5)
Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis, resulting in the development of a colon cancer known as colitis-associated colorectal cancer (CAC). In this study, we evaluated the effects of corylin in a mouse model of dextran sodium sulfate (DSS)-induced colitis. The results showed corylin could improved the survival rate and colon length, maintained body weight, and ameliorated the inflammatory response in the colon. Then, we further identified the possible antitumor effects after 30-day treatment of corylin on an azoxymethane (AOM)/DSS-induced CAC mouse model. Biomarkers associated with inflammation, the colon tissue barrier, macrophage polarization (CD11c, CCR7, CD163, and CD206), and microbiota dysbiosis were monitored in the AOM/DSS group versus corylin groups. Corylin downregulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) mRNA expression and inflammatory signaling-associated markers (TLR4, MyD88, AP-1, CD11b, and F4/80). In addition, a colon barrier experiment revealed that epithelial cell proliferation of the mucus layer (Lgr5, Cyclin D1, and Olfm4) was downregulated and tight junction proteins (claudin-1 and ZO-1) were upregulated. Furthermore, the Firmicutes/Bacteroidetes ratio changed with corylin intervention, and the microbial diversity and community richness of the AOM/DSS mice were improved by corylin. The comparative analysis of gut microbiota revealed that Bacteroidetes, Patescibacteria, Candidatus Saccharimonas, Erysipelatoclostridium, and Enterorhabdus were significantly increased but Firmicutes, Turicibacter, Romboutsia, and Blautia decreased after corylin treatment. Altogether, corylin administration showed cancer-ameliorating effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Therefore, corylin could be a novel, potential health-protective, natural agent against CAC. 相似文献
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Xun-Liang Zou De-An Pei Ju-Zhen Yan Gang Xu Ping Wu 《International journal of molecular sciences》2014,15(4):6592-6608
Zinc finger protein A20 is a key negative regulator of inflammation. However, whether A20 may affect inflammation during peritoneal dialysis (PD)-associated peritonitis is still unclear. This study was aimed to investigate the effect of A20 overexpression on lipopolysaccharide (LPS)-induced inflammatory response in rat peritoneal mesothelial cells (RPMCs). Isolated and cultured RPMCs in vitro. Plasmid pGEM-T easy-A20 was transfected into RPMCs by Lipofectamine™2000. The protein expression of A20, phospho-IκBα, IκBα, TNF receptor-associated factor (TRAF) 6 and CD40 were analyzed by Western blot. The mRNA expression of TRAF6, CD40, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by real time-PCR. NF-κB p65 DNA binding activity, IL-6 and TNF-α levels in cells culture supernatant were determined by ELISA. Our results revealed that RPMCs overexpression of A20 lead to significant decrease of LPS-induced IκBα phosphorylation and NF-κB DNA binding activity (all p < 0.01). In addition, A20 also attenuated the expression of TRAF6, CD40, IL-6 and TNF-α as well as levels of IL-6 and TNF-α in cells culture supernatant (all p < 0.05). However, A20 only partly inhibited CD40 expression. Our study indicated that A20 overexpression may depress the inflammatory response induced by LPS in cultured RPMCs through negatively regulated the relevant function of adaptors in LPS signaling pathway. 相似文献
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Adipose tissue expansion is strongly associated with increased adipose macrophage infiltration and adipocyte-derived pro-inflammatory cytokines, contributing to obesity-associated low-grade inflammation. Individuals with vitamin D deficiency have an increased prevalence of obesity and increased circulating inflammatory cytokines. However, the effect of vitamin D supplementation on obesity-induced inflammation remains controversial. Male C57BL/6J mice received a low-fat (10% fat) or high-fat (HF, 60% fat diet) containing 1000 IU vitamin D/kg diet, or HF supplemented with 10,000 IU vitamin D/kg diet for 16 weeks (n = 9/group). Vitamin D supplementation did not decrease HF-increased body weight but attenuated obesity-induced adipose hypertrophy and macrophage recruitment as demonstrated by the number of crown-like structures. Vitamin D supplementation significantly reduced the mRNA expression of CD11c, CD68, and iNOS, specific for inflammatory M1-like macrophages, and decreased serum levels of NO. In addition, significant reductions in pro-inflammatory gene expression of IL-6, MCP-1, and TNFα and mRNA levels of ASC-1, CASP1, and IL-1β involved in NLRP3 inflammasome were found in obese mice supplemented with vitamin D. Vitamin D supplementation significantly increased obesity-decreased AMPK activity and suppressed HF-increased NF-κB phosphorylation in adipose tissue from obese mice. These observed beneficial effects of vitamin D supplementation on adipose tissue expansion, macrophage recruitment, and inflammation might be related to AMPK/NF-κB signaling. 相似文献
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Katarzyna Tonecka Agata Braniewska Zofia Pilch Zuzanna Sas Marcin Skorzynski Elisabetta Manuali Tomasz P. Rygiel 《International journal of molecular sciences》2021,22(10)
Inflammatory bowel disease is characterized by the infiltration of immune cells and chronic inflammation. The immune inhibitory receptor, CD200R, is involved in the downregulation of the activation of immune cells to prevent excessive inflammation. We aimed to define the role of CD200R ligand-CD200 in the experimental model of intestinal inflammation in conventionally-reared mice. Mice were given a dextran sodium sulfate solution in drinking water. Bodyweight loss was monitored daily and the disease activity index was calculated, and a histological evaluation of the colon was performed. TNF-α production was measured in the culture of small fragments of the distal colon or bone marrow-derived macrophages (BMDMs) cocultured with CD200+ cells. We found that Cd200−/− mice displayed diminished severity of colitis when compared to WT mice. Inflammation significantly diminished CD200 expression in WT mice, particularly on vascular endothelial cells and immune cells. The co-culture of BMDMs with CD200+ cells inhibited TNF-α secretion. In vivo, acute colitis induced by DSS significantly increased TNF-α secretion in colon tissue in comparison to untreated controls. However, Cd200−/− mice secreted a similar level of TNF-α to WT mice in vivo. CD200 regulates the severity of DSS-induced colitis in conventionally-reared mice. The presence of CD200+ cells decreases TNF-α production by macrophages in vitro. However, during DDS-induced intestinal inflammation secretion of TNF-α is independent of CD200 expression. 相似文献
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Lian-Hong Chen Jia-Le Song Yu Qian Xin Zhao Hua-Yi Suo Jian Li 《International journal of molecular sciences》2014,15(1):817-829
The preventive effect of polysaccharide of Larimichthys crocea swimming bladder (PLCSB) and the increase of this effect by use of resistant starch (RS3) as the carrier for PLCSB on azoxymethane (AOM) and dextran sulfate sodium (DSS)-inducing colon carcinogenesis in C57BL/6 mice has been studied. RS3 microspheres carrying PLCSB (RS3 + PLCSB) were produced and evaluated as a potentially improved colon carcinogenesis therapy for this study. The body weight, colon length, and colon weight of mice were determined, and colonic tissues were histologically observed. The serum levels of proinflammatory cytokines and the inflammation and apoptosis-related genes in colonic tissue were also tested. The PLCSB or RS3 + PLCSB significantly suppressed AOM and DSS-induced body weight loss, colon length shortening and decreased the colon weight to length ratio. PLCSB or RS3 + PLCSB reduced the levels of the serum pro-inflammatory cytokines IL-6, IL-12, TNF-α, and IFN-γ to a greater extent compared with the control mice, and the levels of RS3 + PLCSB were more close to the normal mice than PLCSB treated mice. Histopathological examination of sections of colon tissues showed that the RS3 + PLCSB group recovered well from colon carcinogenesis; however, the tissue sections of the stachyose + starch could reduce the necrosis degree. PLCSB significantly induced apoptosis in tissues of mice (p < 0.05) by up-regulating Bax, caspase-3, and caspase-9, and down-regulating Bcl-2. The expression of genes associated with inflammation-related NF-κB, iNOS, and COX-2 genes, was significantly down-regulated, and IκB-α was up-regulated (p < 0.05). These results suggest that PLCSB is a potent preventive against in vivo colon carcinogenesis and that PLCSB with an RS3 carrier could increase the preventative effect in mice. 相似文献
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Itzel Medina-Andrade Jonadab E. Olguín Stephanie Guerrero-García Jossael A. Espinosa Elizabeth Garduo-Javier Victoria Hernndez-Gmez Felipe Vaca-Paniagua Miriam Rodríguez-Sosa Luis I. Terrazas 《International journal of molecular sciences》2021,22(20)
A close connection between inflammation and the risk of developing colon cancer has been suggested in the last few years. It has been estimated that patients diagnosed with some types of inflammatory bowel disease, such as ulcerative colitis or Crohn’s disease, have up to a 30% increased risk of developing colon cancer. However, there is also evidence showing that the activation of anti-inflammatory pathways, such as the IL-4 receptor-mediated pathway, may favor the development of colon tumors. Using an experimental model of colitis-associated colon cancer (CAC), we found that the decrease in tumor development in global IL4Rα knockout mice (IL4RαKO) was apparently associated with an inflammatory response mediated by the infiltration of M1 macrophages (F480+TLR2+STAT1+) and iNOS expression in colon tissue. However, when we developed mice with a specific deletion of IL4Rα in macrophages (LysMcreIL4Rα−/lox mice) and subjected them to CAC, it was found that despite presenting a large infiltration of M1 macrophages into the colon, these mice were as susceptible to colon-tumorigenesis as WT mice. These data suggest that in the tumor microenvironment the absence of IL4Rα expression on macrophages, as well as the recruitment of M1 macrophages, may not be directly associated with resistance to developing colon tumors. Therefore, it is possible that IL4Rα expression in other cell types, such as colonic epithelial cells, could have an important role in promoting the development of colitis-associated colon tumorigenesis. 相似文献
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Gesa Martius Silke Cameron Margret Rave-Fr?nk Clemens F. Hess Hendrik A. Wolff Ihtzaz A. Malik 《International journal of molecular sciences》2015,16(3):4682-4697
Previously, we reported a radiation-induced inflammation triggering fat-accumulation through fatty-acid-translocase/cluster of differentiation protein 36 (FAT/CD36) in rat liver. Furthermore, inhibition of radiation-induced FAT/CD36-expression by anti-tumor necrosis factor-α (anti-TNF-α) (infliximab) was shown in vitro. The current study investigates fat-accumulation in a mouse-model of single-dose liver-irradiation (25-Gray) and the effect of anti-TNF-α-therapy on FAT/CD36 gene-expression. Mice livers were selectively irradiated in vivo in presence or absence of infliximab. Serum- and hepatic-triglycerides, mRNA, and protein were analyzed by colorimetric assays, RT-PCR, Immunofluorescence and Western-Blot, respectively. Sudan-staining was used demonstrating fat-accumulation in tissue. In mice livers, early (1–3 h) induction of TNF-α-expression, a pro-inflammatory cytokine, was observed. It was followed by elevated hepatic-triglyceride level (6–12 h), compared to sham-irradiated controls. In contrast, serum-triglyceride level was decreased at these time points. Similar to triglyceride level in mice livers, Sudan staining of liver cryosections showed a quick (6–12 h) increase of fat-droplets after irradiation. Furthermore, expression of fat-transporter-protein FAT/CD36 was increased at protein level caused by radiation or TNF-α. TNF-α-blockage by anti-TNF-α showed an early inhibition of radiation-induced FAT/CD36 expression in mice livers. Immunohistochemistry showed basolateral and cytoplasmic expression of FAT/CD36 in hepatocytes. Moreover, co-localization of FAT/CD36 was detected with α-smooth muscle actin (α-SMA+) cells and F4/80+ macrophages. In summary, hepatic-radiation triggers fat-accumulation in mice livers, involving acute-phase-processes. Accordingly, anti-TNF-α-therapy prevented early radiation-induced expression of FAT/CD36 in vivo. 相似文献
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You-Chang Oh Yun Hee Jeong Won-Kyung Cho Jeong-Ho Ha Min Jung Gu Jin Yeul Ma 《International journal of molecular sciences》2015,16(1):1232-1251
Pyeongwisan (PW) is an herbal medication used in traditional East Asian medicine to treat anorexia, abdominal distension, borborygmus and diarrhea caused by gastric catarrh, atony and dilatation. However, its effects on inflammation-related diseases are unknown. In this study, we investigated the biological effects of PW on lipopolysaccharide (LPS)-mediated inflammation in macrophages and on local inflammation in vivo. We investigated the biological effects of PW on the production of inflammatory mediators, pro-inflammatory cytokines and related products as well as the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated macrophages. Additionally, we evaluated the analgesic effect on the acetic acid-induced writhing response and the inhibitory activity on xylene-induced ear edema in mice. PW showed anti-inflammatory effects by inhibiting the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and interleukin-1β (IL-1β). In addition, PW strongly suppressed inducible nitric oxide synthase (iNOS), a NO synthesis enzyme, induced heme oxygenase-1 (HO-1) expression and inhibited NF-κB activation and MAPK phosphorylation. Also, PW suppressed TNF-α, IL-6 and IL-1β cytokine production in LPS-stimulated peritoneal macrophage cells. Furthermore, PW showed an analgesic effect on the writhing response and an inhibitory effect on mice ear edema. We demonstrated the anti-inflammatory effects and inhibitory mechanism in macrophages as well as inhibitory activity of PW in vivo for the first time. Our results suggest the potential value of PW as an inflammatory therapeutic agent developed from a natural substance. 相似文献
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Sara Notararigo Encarnacin Varela Anna Otal María Antolín Francisco Guarner Paloma Lpez 《International journal of molecular sciences》2022,23(3)
Bacterial β-glucans are exopolysaccharides (EPSs), which can protect bacteria or cooperate in biofilm formation or in bacterial cell adhesion. Pediococcus parvulus 2.6 is a lactic acid bacterium that produces an O-2-substituted (1-3)-β-D-glucan. The structural similarity of this EPS to active compounds such as laminarin, together with its ability to modulate the immune system and to adhere in vitro to human enterocytes, led us to investigate, in comparison with laminarin, its potential as an immunomodulator of in vitro co-cultured Caco-2 and PMA-THP-1 cells. O-2-substituted (1-3)-β-D-glucan synthesized by the GTF glycosyl transferase of Pediococcus parvulus 2.6 or that by Lactococcus lactis NZ9000[pGTF] were purified and used in this study. The XTT tests revealed that all β-glucans were non-toxic for both cell lines and activated PMA-THP-1 cells’ metabolisms. The O-2-substituted (1-3)-β-D-glucan modulated production and expression of IL-8 and the IL-10 in Caco-2 and PMA-THP-1 cells. Laminarin also modulated cytokine production by diminishing TNF-α in Caco-2 cells and IL-8 in PMA-THP-1. All these features could be considered with the aim to produce function foods, supplemented with laminarin or with another novel β-glucan-producing strain, in order to ameliorate an individual’s immune system response toward pathogens or to control mild side effects in remission patients affected by inflammatory bowel diseases. 相似文献
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Aleksandra Szczepkowska Maciej Wjcik Dorota Tomaszewska-Zaremba Hanna Antushevich Agata Krawczyska Wiktoria Wiechetek Janina Skipor Andrzej Przemysaw Herman 《International journal of molecular sciences》2021,22(24)
This study was designed to determine the effect of acute caffeine (CAF) administration, which exerts a broad spectrum of anti-inflammatory activity, on the synthesis of pro-inflammatory cytokines and their receptors in the hypothalamus and choroid plexus (ChP) during acute inflammation caused by the injection of bacterial endotoxin—lipopolysaccharide (LPS). The experiment was performed on 24 female sheep randomly divided into four groups: control; LPS treated (iv.; 400 ng/kg of body mass (bm.)); CAF treated (iv.; 30 mg/kg of bm.); and LPS and CAF treated. The animals were euthanized 3 h after the treatment. It was found that acute administration of CAF suppressed the synthesis of interleukin (IL-1β) and tumor necrosis factor (TNF)α, but did not influence IL-6, in the hypothalamus during LPS-induced inflammation. The injection of CAF reduced the LPS-induced expression of TNF mRNA in the ChP. CAF lowered the gene expression of IL-6 cytokine family signal transducer (IL6ST) and TNF receptor superfamily member 1A (TNFRSF1) in the hypothalamus and IL-1 type II receptor (IL1R2) in the ChP. Our study on the sheep model suggests that CAF may attenuate the inflammatory response at the hypothalamic level and partly influence the inflammatory signal generated by the ChP cells. This suggests the potential of CAF to suppress neuroinflammatory processes induced by peripheral immune/inflammatory challenges. 相似文献
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Wei Li Tianyi Liu Liangliang Wu Chun Chen Zhiwei Jia Xuedong Bai Dike Ruan 《International journal of molecular sciences》2014,15(10):17270-17283
The debilitating effects of lower back pain are a major health issue worldwide. A variety of factors contribute to this, and oftentimes intervertebral disk degeneration (IDD) is an underlying cause of this disorder. Inflammation contributes to IDD, and inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, play key roles in the pathology of IDD. Therefore, the development of treatments that inhibit the expression and/or effects of TNF-α and IL-1β in IDD patients should be a promising therapeutic approach to consider. This study characterized the potential to suppress inflammatory cytokine production in degenerative intervertebral disc (NP) cells by treatment with IL-10 and TGF-β in a canine model of IDD. IDD was induced surgically in six male beagles, and degenerative NP cells were isolated and cultured for in vitro studies on cytokine production. Cultured degenerative NP cells were divided into four experimental treatment groups: untreated control, IL-10-treated, TGF-β-treated, and IL-10- plus TGF-β-treated cells. Cultured normal NP cells served as a control group. TNF-α expression was evaluated by fluorescence activated cell sorting (FACS) analysis and enzyme-linked immunosorbent assay (ELISA); moreover, ELISA and real-time PCR were also performed to evaluate the effect of IL-10 and TGF-β on NP cell cytokine expression in vitro. Our results demonstrated that IL-10 and TGF-β treatment suppressed the expression of IL-1β and TNF-α and inhibited the development of inflammatory responses. These data suggest that IL-10 and TGF-β should be evaluated as therapeutic approaches for the treatment of lower back pain mediated by IDD. 相似文献
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Jiang Pu Fan-Fu Fang Xiu-Qing Li Zhi-Heng Shu Yi-Ping Jiang Ting Han Wei Peng Cheng-Jian Zheng 《International journal of molecular sciences》2016,17(9)
To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway. 相似文献
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Alexandra Wetzel Bettina Scholtka Fabian Schumacher Harshadrai Rawel Birte Geisendrfer Burkhard Kleuser 《International journal of molecular sciences》2021,22(10)
Ulcerative colitis (UC), a severe chronic disease with unclear etiology that is associated with increased risk for colorectal cancer, is accompanied by dysregulation of cytokines. Epstein–Barr virus-induced gene 3 (EBI3) encodes a subunit in the unique heterodimeric IL-12 cytokine family of either pro- or anti-inflammatory function. After having recently demonstrated that upregulation of EBI3 by histone acetylation alleviates disease symptoms in a dextran sulfate sodium (DSS)-treated mouse model of chronic colitis, we now aimed to examine a possible further epigenetic regulation of EBI3 by DNA methylation under inflammatory conditions. Treatment with the DNA methyltransferase inhibitor (DNMTi) decitabine (DAC) and TNFα led to synergistic upregulation of EBI3 in human colon epithelial cells (HCEC). Use of different signaling pathway inhibitors indicated NFκB signaling was necessary and proportional to the synergistic EBI3 induction. MALDI-TOF/MS and HPLC-ESI-MS/MS analysis of DAC/TNFα-treated HCEC identified IL-12p35 as the most probable binding partner to form a functional protein. EBI3/IL-12p35 heterodimers (IL-35) induce their own gene upregulation, something that was indeed observed in HCEC cultured with media from previously DAC/TNFα-treated HCEC. These results suggest that under inflammatory and demethylating conditions the upregulation of EBI3 results in the formation of anti-inflammatory IL-35, which might be considered as a therapeutic target in colitis. 相似文献