scholarly journals Novel Compound Q-1 Alleviates Type II Collagen-Induced Arthritis in Rats through the NF-κB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Ting Xu ◽  
Jia-Chen Guo ◽  
Sha-Sha Wu ◽  
Yan Wang ◽  
Xiao-Long Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ankle Joint ◽  
Liver Homogenate ◽  
Type Ii Collagen ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Type Ii ◽  
Collagen Induced Arthritis ◽  
Protein Levels

Background. Q-1 is a novel compound extracted from the Miao medicine Tiekuaizi. Although Q-1 is known to be a coumarin derivative, its structure has not been deposited in the ACX library. Our previous study showed that Q-1 inhibits the activity of inflammatory cells. This study explores the efficacy of Q-1 in regulating rheumatoid arthritis (RA). The findings show that Q-1 acts through the NF-κB signaling pathway. Methods. The effects of Q-1 were explored using a bovine type II collagen-induced arthritis (CIA) rat model. The CIA rats were intragastrically administered with high (30 mg·kg−1) or low (15 mg·kg−1) doses of Q-1. The control group was administered with an equal volume of drinking water, while the positive control group was administered with Tripterygium glycoside (9.45 mg·kg−1) for 28 consecutive days. The arthritis indices and ankle joint swelling rates were determined. The levels of IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1) in serum and sialic acid (SA) in liver homogenate were determined by enzyme-linked immunosorbent assay (ELISA). The pathological features of the ankle joint were analyzed by hematoxylin and eosin (HE) staining. The IκB, P-IκB, P65, and P-P65 protein levels in synovial tissue were assayed by western blotting. Results. The arthritis index, ankle joint swelling rate, IL-1β, IL-6, and MCP-1 levels in serum, SA level in liver tissue, and IκB, P-IκB, P65, and P-P65 protein levels in synovial tissues were significantly higher ( P < 0.01 ) in the CIA model compared to the control group. RA was successfully replicated by the CIA model, as shown by the joint swelling results and histopathological sections of the ankle. Notably, all the above indicators decreased significantly ( P < 0.01 ) after treatment with Q-1 compared to the model. In addition, animals treated with Q-1 showed lower inflammation in the ankle joints than the model rats. Conclusion. The findings indicate that Q-1 effectively inhibited RA in rats by downregulating IκB, P-IκB, P65, and P-P65, inhibiting the excessive release of inflammatory factors, and inhibiting the overactivation of the NF-κB signaling pathway.

scholarly journals Immunoregulatory Role of MicroRNA-21 in Macrophages in Response to Bacillus Calmette-Guerin Infection Involves Modulation of the TLR4/MyD88 Signaling Pathway

2017 ◽  
Vol 42 (1) ◽  
pp. 91-102 ◽  
Author(s):  
Xin Xue ◽  
Yi Qiu ◽  
Hong-Li Yang
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Bacillus Calmette Guerin ◽  
Myd88 Signaling ◽  
Apoptosis And Necrosis

Background/Aims: The purpose of this study is to explore the immunoregulatory role of microRNA-21 (miR-21) targeting of the TLR4/MyD88 signaling pathway in macrophages in response to Bacillus Calmette-Guerin (BCG) infection. Methods: After infection with BCG, mouse RAW246.7 cells were assigned into control, BCG, miR-21 mimic + BCG, mimic-negative control (NC) + BCG, miR-21 inhibitor + BCG, inhibitor-NC + BCG, BCG + TAK242 (an inhibitor of the TLR4 signaling pathway), and miR-21 inhibitor + TAK242 + BCG groups. Western blotting and qRT-PCR were used to detect the expression of miR-21, TLR4 and MyD88. The levels of TNF-a, IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Cell viability was measured using an MTT assay. Cell apoptosis and necrosis rates were detected using flow cytometry. Results: Compared with the control group, miR-21 expression and levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were elevated, while expression of TLR4 and MyD88, as well as cell viability, were reduced in BCG infection groups. Compared with the BCG group, miR-21 expression was increased in the miR-21 mimic + BCG group but decreased in the miR-21 inhibitor + BCG and miR-21 inhibitor + TAK242 + BCG groups. The expression of TLR4 and MyD88, as well as the cell viability, were decreased, while levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were increased in the miR-21 mimic + BCG and TAK242 + BCG groups. The opposite trends were found in the miR-21 inhibitor + BCG group. Compared with the TAK242 + BCG group, the miR-21 inhibitor + TAK242 + BCG group had higher expression of TLR4 and MyD88 as well as higher cell viability and lower levels of TNF-a, IL-6, IL-10, cell apoptosis and necrosis rates. However, the miR-21 inhibitor + TAK242 + BCG group exhibited the opposite trends when compared with the miR-21 inhibitor + BCG group. Conclusion: Our results suggest that miR-21 can negatively modulate the TLR4/MyD88 signaling pathway, resulting in decreased cell viability, increased cell apoptosis and increased levels of inflammatory factors following BCG infection in macrophages.

scholarly journals IL-38 restrains inflammatory response of collagen-induced arthritis in rats via SIRT1/HIF-1α signaling pathway

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Bing Pei ◽  
Keyan Chen ◽  
Shenglai Zhou ◽  
Dongyu Min ◽  
Weiguo Xiao
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Joint Damage ◽  
Inhibitory Effect ◽  
Angiogenic Factor ◽  
Inflammatory Factors ◽  
Control Group ◽  
Collagen Induced Arthritis ◽  
Related Proteins

Abstract Objective: To observe the restraining effect of IL-38 on inflammatory response in collagen-induced arthritis rats (CIA), and to explore the regulatory mechanism of SIRT1/HIF-1α signaling pathway. Methods: 40 SD rats were randomly divided into Control group, CIA group, CLL group and CLH group, with 10 rats in each group; CIA rat model was established. The effects of IL-38 on arthritis index, inflammatory response, osteogenic factor and angiogenic factor were observed by methods including HE staining, ELISA, immunohistochemical and immunofluorescence. Human synoviocytes were cultured in vitro, and SIRT1 inhibitors were added to detect the expression for relating factors of SIRT1/HIF-1α signaling pathway by Western blot. Results: IL-38 could alleviate CIA joint damage and restrain inflammatory response, could up-regulate the expression of OPG in CIA rats and could down-regulate the expression of RANKL and RANK. IL-38 could restrain the expression of VEGF, VEGFR1, VEGFR2 and HIF. Moreover, we found that IL-38 could up-regulate the SIRT1 expression and down-regulate the HIF-1α, TLR4 and NF-KB p65 expression in CLL and CLH groups. From the treatment of synoviocytes to simulate the CIA model and the treatment of SIRT1 inhibitors, we demonstrated that the inhibitory effect of IL-38 on inflammatory factors and regulation of SIRT1/HIF-1α signaling pathway-related proteins were inhibited. Conclusion: IL-38 can restrain the inflammatory response of CIA rats, can promote the expression of osteogenic factors, can inhibit neovascularization, and can alleviate joint damage in rats. The mechanism may be related to the regulation of SIRT1/HIF-1α signaling pathway.

scholarly journals Serum changes in pyridinoline, type II collagen cleavage neoepitope and osteocalcin in early stage male brucellosis patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Qiang Li ◽  
Lansheng Hu ◽  
Zhijun Zhao ◽  
Li Ma ◽  
Jiquan Li ◽  
...  
Keyword(s):  
Early Stage ◽  
Venous Blood ◽  
Type Ii Collagen ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Human Brucellosis ◽  
Type Ii ◽  
Median Serum ◽  
Control Study

Abstract Musculoskeletal changes are the most common clinical manifestation of brucellosis. The main objective of this study was to provide a better understanding of this disease, while also attempting to identify potential markers that can identify the early stage musculoskeletal changes associated with human brucellosis. In this case–control study, 41 male early-stage brucellosis patients (within 6 months of diagnosis) who had not received drug therapy and 44 matched controls were examined. Venous blood samples were collected and serum pyridinoline (PYD), type II collagen cleavage neoepitope (C2C) and osteocalcin (OC) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). In the brucellosis group, the median serum levels of PYD (278.53 µg/L), C2C (82.23 µg/L) and OC (8.41 µg/L) were significantly elevated relative to the control group (Z = 5.686, 3.997, 3.579; P = 0.000). Serum PYD, C2C, and OC levels were increased in early-stage male brucellosis patients, and these factors appear to have promise as potential indicator biomarkers that can reflect the osteoarticular changes that occur in the early stage of human brucellosis.

scholarly journals Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Hiroyuki Yamada ◽  
Hiroshi Mori ◽  
Yasutomo Nakanishi ◽  
Satoshi Nishikawa ◽  
Yasuaki Hashimoto ◽  
...  
Keyword(s):  
Joint Destruction ◽  
Cathepsin K ◽  
Type Ii Collagen ◽  
Control Group ◽  
Type I ◽  
Type Ii ◽  
Collagen Induced Arthritis ◽  
Cynomolgus Monkeys ◽  
X Ray ◽  
Cathepsin K Inhibitor

We examined whether the cathepsin K inhibitor, ONO-5334, administered alone or in combination with methotrexate (MTX), could ameliorate joint destruction evoked by collagen-induced arthritis (CIA) in female cynomolgus monkeys. CIA was induced by immunizing with bovine type II collagen. ONO-5334 (30 mg/kg/day) was orally administered once daily and MTX (10 mg/body/day) twice weekly for 9 weeks. X-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal (PIP), distal interphalangeal (DIP), and metacarpophalangeal (MP) joints were evaluated. Urinary concentrations of C-terminal telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) were measured. Arthritis, accompanied by bone and cartilage destruction, was successfully induced in this collagen-induced arthritis monkey model. ONO-5334 showed no suppressive effect on joint swelling, while the joint swelling scores in the MTX and combination (ONO-5334 + MTX) groups were less than 50% compared with the control group. ONO-5334 decreased X-ray score by a mean of 64% (p<0.05 vs the control group), and MTX also decreased in X-ray score by a mean of 46% but with no statistical significance. Combination of ONO-5334 and MTX further decreased the X-ray score by 28% over MTX group (74% reduction vs the control group, p<0.01). Maximum increase in CTX-I (10-fold) and CTX-II (7-fold) compared to baseline was observed at 7 and 3 weeks after the first sensitization, respectively. After treatment with ONO-5334 alone or in combination with MTX, concentrations were maintained near baseline for both markers. In conclusion, ONO-5334 prevented joint destruction but not joint inflammation in this monkey CIA model. Concomitant use of ONO-5334 with MTX reduced architectural joint destruction compared to MTX alone; therefore, ONO-5334 may help to prevent joint destruction in combination with MTX for the treatment of rheumatoid arthritis.

scholarly journals Comparative Evaluation of 68Ga-Citrate PET/CT and 18F-FDG PET/CT in the Diagnosis of Type II Collagen-Induced Arthritis in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Zi Wang ◽  
Liang Cai ◽  
Tingting Xu ◽  
Dan Tang ◽  
Lin Liu ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Type Ii Collagen ◽  
Thigh Muscle ◽  
Control Group ◽  
Late Time ◽  
Type Ii ◽  
Collagen Induced Arthritis ◽  
Pet Ct ◽  
Fdg Pet Ct

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic, symmetrical, and erosive synovitis. RA is one of the most common disabling diseases in the clinic. The main clinical intervention strategies are early diagnosis and early treatment. This study aims to predict the diagnostic value of 68Ga-citrate and 18F-FDG PET/CT in RA by comparing and analyzing the value of 68Ga-citrate and 18F-FDG PET/CT for diagnosing type II collagen-induced arthritis (CIA) in rats. Some CIA models were established. Normal rats were selected as the control group, and 23 days and 40 days were selected as the early and late time points of arthritis, respectively. The semiquantitative analysis of CIA rats was carried out with 68Ga-citrate PET/CT and 18F-FDG PET/CT, and the ratio of the maximum standardized uptake (SUVmax) values in the regions of interest (ROIs) of the hind foot ankle joint and thigh muscle was calculated and statistically analyzed. The distribution of CIA rats in vivo at the 68Ga-citrate 90 min time point was studied, and the ankle tissues were evaluated with hematoxylin and eosin (HE) staining. 68Ga-citrate PET/CT is obviously superior to 18F-FDG PET/CT for CIA imaging, and the statistical results show that the difference between the two examination methods is statistically significant (P<0.001). The uptake of these two radiopharmaceuticals showed the same trend in arthritis rats with different scores. The distribution of 68Ga-citrate at 90 min is consistent with the trend shown by 68Ga-citrate PET/CT. 68Ga-citrate PET/CT can reflect the inflammatory activity of affected joints in CIA rats earlier and more sensitively than 18F-FDG PET/CT, and this imaging advantage continues until the later stage of inflammation. Therefore, 68Ga-citrate PET/CT is worthy of further promotion and application in the clinical diagnosis of RA.

LncRNA NEAT1 promotes inflammatory response and induces corneal neovascularization

2018 ◽  
Vol 61 (4) ◽  
pp. 231-239 ◽  
Author(s):  
Yan-hui Bai ◽  
Yong Lv ◽  
Wei-qun Wang ◽  
Guang-li Sun ◽  
Hao-hao Zhang
Keyword(s):  
Inflammatory Response ◽  
Rat Model ◽  
Noncoding Rna ◽  
Corneal Neovascularization ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Protein Levels ◽  
Lncrna Neat1

Human corneal fibroblasts (HCFs) are implicated in corneal neovascularization (CRNV). The mechanisms underlying the inflammatory response in HCFs and the development of CRNV were explored in this study. Alkali burns were applied to the corneas of rats to establish a CRNV model. The expression of long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) and mRNA and protein levels of nuclear factor kappa B (NF-κB)- activating protein (NKAP) were examined by quantitative real-time (qRT-PCR) and Western blot methods, respectively. Lipopolysaccharide (LPS) is used to stimulate HCFs for inflammatory response. The level of inflammation factors in HCF supernatant was detected using an enzyme-linked immunosorbent assay (ELISA). Binding and interactions between NEAT1 and miRNA 1246 (miR-1246) were determined by RNA immunoprecipitation (RIP) and RNA pull-down assays in HCFs. Compared with the control group (n = 6), NEAT1 was upregulated in the corneas of the CRNV rat model (n = 6). The expression of NEAT1 in HCFs was upregulated by LPS. Downregulation of NEAT1 suppressed the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). NEAT1 could bind and interact with miR-1246. LPS regulated the expression of NKAP and NF-κB signaling via the NEAT1/miR-1246 pathway. Downregulation of NEAT1in vivoinhibited CRNV progression in the CRNV rat model. The lncRNA NEAT1 induced secretion of inflammatory factors, mediated by NF-κB, by targeting miR-1246, thereby promoting CRNV progression.

Anti-inflammatory Effect of Bee Venom on Type II Collagen-Induced Arthritis

2004 ◽  
Vol 32 (03) ◽  
pp. 361-367 ◽  
Author(s):  
Jae-Dong Lee ◽  
Su-Young Kim ◽  
Tae-Woo Kim ◽  
Sang-Hoon Lee ◽  
Hyung-In Yang ◽  
...  
Keyword(s):  
Acupuncture Therapy ◽  
Acupuncture Point ◽  
Type Ii Collagen ◽  
Bee Venom ◽  
Control Group ◽  
Type Ii ◽  
Collagen Induced Arthritis ◽  
Collagen Injection ◽  
Tnf Α ◽  
Anti Inflammatory

Bee venom (BV) has been used to relieve pain and reduce inflammation in traditional Oriental medicine, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). We previously reported that the BV injection into a traditional acupuncture point (Zusanli) reduced arthritis-associated edema and nociceptive responses in Freund's adjuvant-induced arthritis in rats (Kwon et al., 2001). This study was designed to evaluate the anti-inflammatory and anti-cytokine effect of BV on a murine type-II collagen-induced arthritis (CIA) model. Male mice were immunized by spontaneous injection of 100 μg of an emulsion of bovine type-II collagen and complete Freund's adjuvant (CFA), with a booster injection after 2 weeks. In the experimental group, 0.1 ml BV was injected at acupuncture point (Zusanli) near both knees twice a week for a total of 5 times. In the control group, normal saline was injected at the same frequencies. These injections began 5 weeks after the first collagen injection. Starting the 3rd week after the first collagen injection, we examined limb swelling and severity of arthritis twice a week. At 8 weeks, mice were sacrificed and synovial tissue was examined with the light microscope and serum cytokines (IL-1β and TNF-α) were measured by ELISA. The incidence of arthritis, the mean arthritis index and the number of arthritic limbs were significantly lower in the treatment compared to the control group (63% versus 75%, 3.4% versus 8.5%, 23% versus 75%, respectively). Among the serum proinflammatory cytokines, the production of TNF-α in the BV group was suppressed compared to the control group (59+/-4.5 versus 99.5+/-6.5, p <0.05), but IL-1β was not suppressed. The examination of the histopathology of the joints of murine CIA showed decreased inflammation signs and less lymphocyte infiltration after BV acupuncture therapy. Acupuncture therapy with BV suppressed the development of arthritis and caused inhibition of the immune responses in type-II collagen-induced arthritis.

The Effect of Da-Fang-Feng-Tang on Treatment of Type II Collagen-induced Arthritis in DBA/1 Mice

1999 ◽  
Vol 27 (02) ◽  
pp. 205-215 ◽  
Author(s):  
Lian Rong Wang ◽  
Naoki Ishiguro ◽  
Eiji Yamada ◽  
Yoshihiro Nishida ◽  
Koji Sato ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Histological Examination ◽  
Bone Erosion ◽  
Type Ii Collagen ◽  
Treated Group ◽  
Control Group ◽  
Human Rheumatoid Arthritis ◽  
Type Ii ◽  
Collagen Induced Arthritis ◽  
Igg Antibody

Da-Fang-Feng-Tang (DFFr), which is believed to be effective for treating human rheumatoid arthritis (RA), was given to DBA/1 mice at the onset of type II collagen-induced arthritis (CIA) to examine its effect. Granules of the crude DFFT extract were administered by gastric gavage at a dose of 1.6 g/kg/day for 12 weeks, starting the day CIA began. The levels of anticollagen IgG antibody were significantly decreased in the sera of the DFFT-treated group compared with the control group from weeks 2 to 7 after the onset of CIA. The severity of arthritis in the DFFT-treated group was markedly alleviated when compared with the control group. In addition, histological examination of the DFFT-treated group showed less cartilage and bone erosion. These results suggest that administration of DFFT suppressed the development of CIA in mice and support the belief that DFFT is effective in treating human RA.

scholarly journals Thymic Stromal Lymphopoietin Signaling Pathway Inhibition Attenuates Airway Inflammation and Remodeling in Rats with Asthma

2018 ◽  
Vol 47 (4) ◽  
pp. 1482-1496 ◽  
Author(s):  
Zhe  Cheng ◽  
Xi Wang ◽  
Ling-Ling Dai ◽  
Liu-Qun Jia ◽  
Xiao-Gang Jing ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Signaling Pathway ◽  
Airway Remodeling ◽  
Quantitative Polymerase Chain Reaction ◽  
Thymic Stromal Lymphopoietin ◽  
Collagen I ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Protein Levels ◽  
Ifn Γ

Background/Aims: Thymic stromal lymphopoietin (TSLP) is a cytokine that plays diverse roles in the regulation of immune responses. However, a detailed understanding of the TSLP signaling pathway in asthma remains elusive. In this study, we aimed to investigate the role of the TSLP signaling pathway in asthma and its effect on airway inflammation and remodeling. Methods: Forty Sprague Dawley (SD) rats were evenly classified into control, asthma, IgG2a mAb and anti-TSLP mAb groups. Ovalbumin (OVA)-induced asthma models were successfully established. Blood, bronchoalveolar lavage fluid (BALF) and lung tissue samples were prepared. Total BALF leukocytes were counted, and the proportions of different leukocyte types were determined. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to determine the mRNA and protein levels of TSLP, OX40L, α-smooth muscle actin (α-SMA, a marker of airway remodeling in asthma) and collagen I in the plasma. Enzyme-linked immunosorbent assay (ELISA) was carried out to measure the concentrations of TSLP, OX40L, and other inflammatory factors, such as interferon (IFN)-γ, interleukin (IL)-4, IL-5 and IL-13, in the plasma. Results: Compared with the control group, there were more leukocytes, increased EOS and LYM proportions, higher Underwood and PAS scores, increased WTt, WTm, WAt/A0, WAm/WAt, WTt/R0, WTm/WTt, TSLP, OX40L, a-SMA and collagen I mRNA and protein levels, and higher SLP, OX40L, IL-4, IL-5 and IL-13 levels, but lower MON proportions and IFN-γ levels in the asthma and IgG2a mAb groups. Compared with the asthma and IgG2a mAb groups, there were less leukocytes, decreased EOS and LYM proportions, lower Underwood and PAS scores, decreased WTt, WTm, WAt/A0, WAm/WAt, WTt/R0, WTm/WTt, TSLP, OX40L, a-SMA and Collagen I mRNA and protein levels, and lower levels of SLP, OX40L, IL-4, IL-5 and IL-13, but higher MON proportions and IFN-γ levels in the anti-TSLP mAb group. WTm and WTt were positively associated with the TSLP, OX40L, α-SMA and collagen-I levels in the rat lung tissues. Conclusion: The results indicate that TSLP may be an important contributor for asthma development as TSLP signaling blockade attenuates airway inflammation and remodeling in asthmatic rats.

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