CircIFNGR2 regulating ankylosing spondylitis-associated inflammation through macrophage polarization.
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ABSTRACT:
SUBMITTER: Song M
PROVIDER: S-EPMC10372825 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
circIFNGR2 regulating ankylosing spondylitis-associated inflammation through macrophage polarization.
Song Minkai M Wang Xiangyu X Gao Jiawen J Jiang Weizhou W Bi Enguang E An Taixue T Wang Ting T Chen Zishuo Z Liu Weilu W Shi Zhanjun Z Xiao Jun J Zhang Chao C
iScience 20230710 8
Macrophages activation is crucial in pathogenesis of rheumatic diseases like ankylosing spondylitis (AS). Circular RNAs (circRNAs)-induced macrophage-associated inflammation participates in many autoimmune diseases but remains elusive in AS. Here, we verified increased expression of circIFNGR2 in peripheral blood mononuclear cells from patients with AS and its expression levels were correlated with the AS severity. <i>In vitro</i> assays revealed that circIFNGR2 enhances macrophage proliferation ...[more]
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Project description:BackgroundAnkylosing spondylitis (AS) is an autoimmune disease with a genetic correlation and is characterized by inflammation in the axial skeleton and sacroiliac joints. Many AS patients also have inflammatory bowel diseases (IBD), but the underlying causes of intestinal inflammation and osteoporosis in AS are not well understood. CX3CL1, a protein involved in inflammation, has been found to be up-regulated in AS patients and AS-model mice.MethodsThe authors investigated the effects of CX3CL1 on AS by studying its impact on macrophage polarization, inflammation factors, and osteoclast differentiation. Furthermore, the effects of inhibiting the NF-κB pathway and blocking CX3CL1 were assessed using BAY-117082 and anti-CX3CL1 mAb, respectively. AS model mice were used to evaluate the effects of anti-CX3CL1 mAb on limb thickness, spine rupture, and intestinal tissue damage.ResultsThe authors found that CX3CL1 increased the expression of M1-type macrophage markers and inflammation factors, and promoted osteoclast differentiation. This effect was mediated through the NF-κB signaling pathway. Inhibition of the NF-κB pathway prevented M1-type macrophage polarization, reduced inflammation levels, and inhibited osteoclast differentiation. Injection of anti-CX3CL1 mAb alleviated limb thickness, spine rupture, and intestinal tissue damage in AS model mice by inhibiting M1-type macrophage polarization and reducing intestinal tissue inflammation.ConclusionsThe study demonstrated that up-regulated CX3CL1 promotes M1-type macrophage polarization and osteoclast differentiation through the NF-κB signaling pathway. Inhibition of this pathway and blocking CX3CL1 can alleviate inflammation and bone destruction in AS. These findings contribute to a better understanding of the pathogenesis of AS and provide a basis for clinical diagnosis and treatment.
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Project description:BackgroundGlioblastoma is a type of aggressive brain tumor-related to infiltrating microglia/macrophages. Various studies have identified antitumor properties of a bioactive plant compound named honokiol, originating from the Magnolia species. This beneficial characteristic of honokiol has been discovered in many malignant tumors.MethodsWe investigated the molecular mechanisms behind the anti-glioma effects of liposomal honokiol (Lip-HNK) using qRT-PCR, Western blot, co-culture, and in vivo animal experiments.ResultsIt was discovered that the expression of M1 markers such as CD11c, inducible nitric oxide synthase (iNOS), and major histocompatibility complex (MHC) II (IA/IE subregions) induced by lipopolysaccharide (LPS)/IFN-γ was increased by Lip-HNK, and M2 markers Arg1 and CD206 induced by interleukin (IL)-4 had reduced expression, thus inhibiting tumor cell growth through co-culture experiments. After Lip-HNK treatment, a considerable increase in signal transducer and activator of transcription 1 (STAT1) activation was observed, and in contrast, STAT6 activation was suppressed. STAT1 and STAT6 are the key signaling molecules mediating M1 and M2 polarization, respectively. Furthermore, the percentage of CD11c-positive M1 macrophages was increased by Lip-HNK in G422 xenograft mice, while Lip-HNK treatment reduced the CD206-positive M2 macrophage distribution in tumor tissues. These findings are consistent with the decline in tumor volume seen in mice treated with Lip-HNK.ConclusionsLip-HNK inhibits the growth of glioblastoma by upregulating M1 macrophages and limiting M2 phenotypic macrophages.
| S-EPMC8667111 | biostudies-literature
Project description:Mucosal-associated invariant T (MAIT) cells, a novel population of innate-like lymphocytes, have been involved in various inflammatory and autoimmune diseases. However, their role in the development of nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated the alterations of phenotype and immunological function of MAIT cells in NAFLD. Analysis of PBMCs in 60 patients with NAFLD and 48 healthy controls (HC) revealed that circulating MAIT cell frequency decreased in NAFLD, especially in the patients with higher serum levels of γ-glutamyl transferase or total triglyceride. Functional alterations of circulating MAIT cells were also detected in NAFLD patients, such as the increased production of IL-4 whereas the decreased production of IFN-γ and TNF-α. Furthermore, elevated expression of CXCR6 was observed in circulating MAIT cells of patients. Meanwhile, we found an increased number of MAIT cells in the livers of NAFLD, and the number was even greater in patients with higher NAFLD activity score. Moreover, activated MAIT cells induced monocytes/macrophages differentiation into M2 phenotype in vitro. Additionally, MAIT cells were enriched and displayed Th2 type cytokines profile in livers of wild type mice fed with methionine and choline deficient diet (MCD). Notably, mice deficient of MAIT cells exhibited more severe hepatic steatosis and inflammation upon MCD, accompanied with more CD11c+ proinflammatory macrophages (M1) and less CD206+ anti-inflammatory macrophages (M2) in livers. Our results indicate that MAIT cells protect against inflammation in NAFLD through producing regulatory cytokines and inducing anti-inflammatory macrophage polarization, which may provide novel therapeutic strategies for NAFLD.
| S-EPMC6131560 | biostudies-literature
Project description:ObjectiveAnkylosing spondylitis (AS) patients often present with microscopic signs of gut inflammation. We used proteomic techniques to identify the differentially expressed proteins (DEPs) in the colon tissues of patients with AS and patients with gut inflammation, and then used investigated the influence of NMRAL1 protein on inflammatory cytokines to explore its potential role in the pathogenesis of AS and gut inflammation.MethodsColonic mucosal tissues were collected from four different groups: healthy individuals (group A), patients with gut inflammation only (group B), patients with AS only (group C), and patients with AS combined with gut inflammation (group D). A total of 20 samples were processed for proteomic analysis, wherein proteins were extracted using SDT lysis, followed by separation via sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The proteins were digested using the filter-aided sample preparation (FASP) method and then analyzed using a timsTOF Pro mass spectrometer. The resulting peptide data were used to identify differentially expressed proteins (DEPs) across the different groups. To further explore the inflammation-related function of NMRAL1 protein, the murine monocyte/macrophage cell line RAW264.7 was used. NMRAL1 mRNA expression levels were assessed via RT-qPCR, and inflammatory cytokine levels (TNF-α, IL-1β, IL-17 and IL-23) were measured using ELISA following NMRAL1 siRNA transfection in LPS-treated macrophages.ResultsWe collected colonic mucosa specimens from 20 patients, including groups A,B, C and D with 5 patients in each group. We established a database of DEPs and identified 107 (63 upregulated and 44 downregulated) between group B and group A, 78 (16 upregulated and 62 downregulated) between group D and group C, 45 (8 upregulated and 37 downregulated) between group D and group B, and 57 (33 upregulated and 24 downregulated) between group C and group A. Further analysis revealed that the NmrA-like family domain containing 1 (NMRAL1) protein was identified as a DEP specifically associated with group D. The results of in vitro results showed a significant decrease in NMRAL1 mRNA expression in LPS-treated cells (P<0.001), which was further reduced in NMRAL1 siRNA-transfected cells (P<0.0001), confirming successful transfection. ELISA results revealed that the levels of key inflammatory cytokines (TNF-α, IL-1β, IL-17 and IL-23) were significantly elevated in the LPS-treated model group (P<0.0001, P<0.001), but these levels were significantly decreased after NMRAL1 siRNA transfection (P<0.0001, P<0.01, P<0.05).ConclusionNMRAL1 is identified as a key differentially expressed protein in AS patients with gut inflammation. Knockdown of NMRAL1 significantly reduced the levels of inflammatory cytokines, suggesting its potential role in the pathogenesis of AS and gut inflammation, and as a possible therapeutic target.
| S-EPMC11642932 | biostudies-literature
Project description:Genotyping was performed using a custom-designed Illumina 384-SNP VeraCode microarray (Illumina) to determine possible associations of genes encoding PADI1, PADI2, PADI3, PADI4, PADI6, PRKD3, Gc, GLRX,CDSN, PSORS1C1, TXNDC5, CA1, bub3, SORBS1, VDR,SERPNA1, PCSK6, DNAH9 to rheumatoid arthrities (RA) and ankylosing spondylitis (AS). We previously found that encoding genes of PADI1, PADI2, PADI3, PADI4, PADI6, PRKD3, Gc, GLRX,CDSN, PSORS1C1, TXNDC5, CA1, bub3, SORBS1, VDR, SERPNA1, PCSK6 and DNAH9 could be associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We used illumina customer designed microarray to verify the above finding with an increased numbers of samples. Genotyping was performed using a custom-designed Illumina 384-SNP VeraCode microarray (Illumina) to determine possible associations of genes encoding PADI1, PADI2, PADI3, PADI4, PADI6, PRKD3, Gc, GLRX,CDSN, PSORS1C1, TXNDC5, CA1, bub3, SORBS1, VDR, SERPNA1, PCSK6, DNAH9 to RA and AS. A case-control study was performed with 51 AS patients, 266 rheumatoid arthritis (RA) and 163 health controls. Tag single nucleotide polymorphisms (tag SNPs) across the above genes were determined by searching the HapMap database. The tag SNPs were selected on the basis of linkage disequilibrium patterns observed in the Han Chinese in Beijing (CHB) samples that were genotyped as a part of the International HapMap Project. Only SNPs with a minor allele frequency of greater than 5% with a pair-wise r2 ≥ 0.8 in the HapMap were considered. SNPs that were in exons and untranslated regions (UTR), as well as promoters and introns within 500 bp of exons were also selected. Candidate SNPs were submitted to Illumina for a design score. The Illumina Assay Design Tool filtered out SNPs that were not suitable for the Illumina platform. Finally, 382 SNPs with a design score of “1” were selected. 382 SNPs within PADI1, PADI2, PADI3, PADI4, PADI6, PRKD3, Gc, GLRX,CDSN, PSORS1C1, TXNDC5, CA1, bub3, SORBS1, VDR,SERPNA1, PCSK6, DNAH9 encoding genes were selected. Genotyping was performed using Illumina VeraCode microarray in a case-control study including 51 AS patients, 266 rheumatoid arthritis (RA) and 163 health controls We performed genotyping using a custom-designed Illumina 384-SNP VeraCode microarray (Illumina). Peripheral blood samples were collected from patients with RA (n=266, 183 female) and AS (n=51, 10 female). RA patients had a mean age of 51.7 years, while AS patients had a mean age of 35.9 years. A total of 163 (60 female) healthy individuals with a mean age of 48.0 years were blood donors. Blood samples were put into Monovette tubes containing 3.8% sodium citrate. The genotyping was conducted with the BeadXpress Reader using the Illumina VeraCode GoldenGate Assay kit. 500 ng of sample DNA were used per assay. Genotype clustering and calling were performed using BeadStudio software (Genomestudio V2010.2 Genotyping module V1.6) (Illumina). This work was completed at the Beijing Institute of Genomics.
2012-07-22 | E-GEOD-39428 | biostudies-arrayexpress
Project description:ObjectiveHigh disease activity of ankylosing spondylitis (AS) is associated with poor sleep quality The purpose of this study was to identify which of the representative tools for evaluating the disease activity of AS best reflect the quality of sleep.MethodsA total of 107 AS patients were enrolled in the study and the sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) Age, sex, concomitant medication, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, Beck Depression Inventory second edition (BDI-II), Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS)-ESR, ASDAS-CRP, pain visual analog scale, Insomnia Severity Index (ISI), and Epworth Sleepiness Scale (ESS) were analyzed as covariates.ResultsOverall, 65% (70/107) of subjects reported poor sleep quality (PSQI>5) There was a positive correlation between the sleep quality and disease activity as measured by the BASDAI, ASDAS-ESR, and ASDAS-CRP In addition, the BASDAI demonstrated good correlations with ISI, ESS, and BDI-II, respectively However, only BASDAI showed reliable correlation with PSQI among the disease activity parameters of AS (adjusted odd ratio 5.36, p=0.023).ConclusionBASDAI is the most reliable parameter of disease activity associated with the sleep quality in patients with AS.
| S-EPMC10324903 | biostudies-literature
Project description:ObjectivesThis study aims to investigate the relationship between disease activity, dietary phytochemical index (DPI), and serum total oxidant status (TOS) and total antioxidant status (TAS) in patients with ankylosing spondylitis (AS).Patients and methodsBetween August 2020 and January 2021, a total of 37 patients (23 males, 14 females; mean age: 39.3±9.4 years; range, 21 to 61 years) with AS and 36 age-, sex-, and body mass index-matched healthy individuals (24 males, 12 females; mean age: 37.9±8.9 years; range, 20 to 60 years) were included. Serum TAS (μmoLTroloxEq/L) and TOS (μmoL H2O2Eq/L) measurements were performed and the oxidative stress index (OSI) was calculated. Dietary evaluation was made from a one-day dietary record and DPI was calculated.ResultsSerum TAS level in AS patients was significantly lower than the healthy group (p=0.003). Serum TOS level was similar in both groups. The OSI of patients was significantly higher than the controls (p=0.035). The mean DPI, polyunsaturated fatty acid, n-3 fatty acid, and vitamin C intake of patients were significantly lower than controls (p=0.042, p=0.033, and p=0.022, respectively). A moderate positive correlation was found between the TAS level and DPI of the control group (r=0.352, p=0.035). According to medications, no significant difference was seen between the groups in terms of patients' characteristics, DPI, and laboratory tests and there was no correlation between DPI, TAS, TOS, and OSI.ConclusionLower DPI and lower n-3 fatty acid and vitamin C intake in patient group demonstrated that patients with AS should pay more attention to their diet to increase serum antioxidant status.
| S-EPMC9326390 | biostudies-literature
Project description:Chronic overnutrition and obesity induces low-grade inflammation throughout the body. Termed "meta-inflammation," this chronic state of inflammation is mediated by macrophages located within the colon, liver, muscle, and adipose tissue. A sentinel orchestrator of immune activity and homeostasis, macrophages adopt variable states of activation as a function of time and environmental cues. Meta-inflammation phenotypically skews these polarization states and has been linked to numerous metabolic disorders. The past decade has revealed several key regulators of macrophage polarization, including the signal transducer and activator of transcription family, the peroxisome proliferator-activated receptor gamma, the CCAAT-enhancer-binding proteins (C/EBP) family, and the interferon regulatory factors. Recent studies have also suggested that microRNAs and long noncoding RNA influence macrophage polarization. The pathogenic alteration of macrophage polarization in meta-inflammation is regulated by both extracellular and intracellular cues, resulting in distinct secretome profiles. Meta-inflammation-altered macrophage polarization has been linked to insulin insensitivity, atherosclerosis, inflammatory bowel disease, cancer, and autoimmunity. Thus, further mechanistic exploration into the skewing of macrophage polarization promises to have profound impacts on improving global health.
| S-EPMC5776711 | biostudies-other
Project description:It's still unknown how over-hyperplasia of tissue such like new bone formation (NBF) developed in ankylosing spondylitis (AS). We found low level of IL-17A promoted TLR4+MSC1 polarization with suppressed osteogenic differentiation through JAK2/STAT3 pathway, while high level of IL-17A promoted TLR3+MSC2 polarization with enhanced osteogenic differentiation through WNT10b/RUNX2 pathway. Furthermore, both proteoglycan-induced spondylitis (PGISp) mouse model and AS patients without NBF showed MSC1 polarization, up-regulated JAK2/STAT3 pathway and high level of IL-17A (peripherally, but not locally), but those with NBF showed MSC2 polarization, up-regulated WNT10b/RUNX2 pathway and high expression of IL-17A at local site. Results showed NBF of AS was induced by MSC2 polarization that was promoted by high level of IL-17A, and may be treated by suppressing local MSC2 polarization.
| S-EPMC5722540 | biostudies-literature
Project description:Genotyping was performed using a custom-designed Illumina 384-SNP VeraCode microarray (Illumina) to determine possible associations of genes encoding PADI1, PADI2, PADI3, PADI4, PADI6, PRKD3, Gc, GLRX,CDSN, PSORS1C1, TXNDC5, CA1, bub3, SORBS1, VDR,SERPNA1, PCSK6, DNAH9 to rheumatoid arthrities (RA) and ankylosing spondylitis (AS). We previously found that encoding genes of PADI1, PADI2, PADI3, PADI4, PADI6, PRKD3, Gc, GLRX,CDSN, PSORS1C1, TXNDC5, CA1, bub3, SORBS1, VDR, SERPNA1, PCSK6 and DNAH9 could be associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We used illumina customer designed microarray to verify the above finding with an increased numbers of samples. Genotyping was performed using a custom-designed Illumina 384-SNP VeraCode microarray (Illumina) to determine possible associations of genes encoding PADI1, PADI2, PADI3, PADI4, PADI6, PRKD3, Gc, GLRX,CDSN, PSORS1C1, TXNDC5, CA1, bub3, SORBS1, VDR, SERPNA1, PCSK6, DNAH9 to RA and AS. A case-control study was performed with 51 AS patients, 266 rheumatoid arthritis (RA) and 163 health controls. Tag single nucleotide polymorphisms (tag SNPs) across the above genes were determined by searching the HapMap database. The tag SNPs were selected on the basis of linkage disequilibrium patterns observed in the Han Chinese in Beijing (CHB) samples that were genotyped as a part of the International HapMap Project. Only SNPs with a minor allele frequency of greater than 5% with a pair-wise r2 ≥ 0.8 in the HapMap were considered. SNPs that were in exons and untranslated regions (UTR), as well as promoters and introns within 500 bp of exons were also selected. Candidate SNPs were submitted to Illumina for a design score. The Illumina Assay Design Tool filtered out SNPs that were not suitable for the Illumina platform. Finally, 382 SNPs with a design score of “1” were selected.
2012-07-23 | GSE39428 | GEO