scholarly journals Children with oligoarticular Juvenile Idiopathic Arthritis have skewed synovial monocyte polarization pattern with functional impairment – a distinct inflammatory pattern for oligoarticular juvenile arthritis

2020 ◽  
Author(s):  
Tobias Schmidt ◽  
Elisabet Berthold ◽  
Sabine Arve-Butler ◽  
Birgitta Gullstrand ◽  
Anki Mossberg ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Mrna Expression ◽  
Mrna Level ◽  
Western World ◽  
Polarization Pattern ◽  
Oligoarticular Juvenile Idiopathic Arthritis ◽  
Monocytes And Macrophages ◽  
Anti Inflammatory

Abstract Background Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JIA is less studied. Polarization highly influences monocytes’ and macrophages’ effector functions, broadly separated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Here, we set out to investigate the polarization pattern and functional aspects of synovial monocytes in oligoarticular juvenile idiopathic arthritis (JIA). Methods Paired synovial fluid, blood samples (n=13) and synovial biopsies (n=3) were collected from patients with untreated oligoarticular JIA. Monocytes were analyzed for polarization markers by flow cytometry and qPCR. Effector function was analyzed by a phagocytosis assay. Polarization of healthy monocytes was investigated by stimulation with synovial fluid in vitro . Monocyte/macrophage distribution, polarization and mRNA expression were investigated in biopsies by immunohistochemistry, immunofluorescence and in situ hybridization. Results Children with oligoarticular JIA have polarized synovial fluid monocytes of a specific M1(IFNγ)/M2(IL-4)-like pattern. This was evidenced by increased surface expression of CD40 (p<0.001), CD86 (p<0.001) and CD206 (p<0.001), but not CD163, as compared to paired circulating monocytes. Additionally, polarization was extensively explored at the mRNA level and synovial fluid monocytes differentially expressed classical markers of M1(IFNγ)/M2(IL-4) polarization compared to circulating monocytes. Synovial fluid monocytes were functionally affected, as assessed by reduced capacity to phagocytose (p<0.01). Synovial fluid induced M2 markers (CD16 and CD206), but not M1 (CD40) or CD86 in healthy monocytes and did not induce cytokine production. Single and co-expression of surface CD40 and CD206, as well as mRNA expression of IL-10 and TNF, was observed in monocytes/macrophages in synovial biopsies. Conclusion Children with untreated oligoarticular JIA have similar and distinct synovial fluid monocyte polarization pattern of mixed pro- and anti-inflammatory features. This pattern was not exclusively a result of the synovial fluid milieu as monocytes/macrophages in the synovial membrane show similar patterns. Our study highlights a distinct polarization pattern in oligoarticular JIA, which could be utilized for future treatment strategies.

scholarly journals Children with oligoarticular Juvenile Idiopathic Arthritis have skewed synovial monocyte polarization pattern with functional impairment – a distinct inflammatory pattern for oligoarticular juvenile arthritis

2020 ◽  
Author(s):  
Tobias Schmidt ◽  
Elisabet Berthold ◽  
Sabine Arve-Butler ◽  
Birgitta Gullstrand ◽  
Anki Mossberg ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Mrna Expression ◽  
Mrna Level ◽  
Western World ◽  
Polarization Pattern ◽  
Oligoarticular Juvenile Idiopathic Arthritis ◽  
Monocytes And Macrophages ◽  
Anti Inflammatory

Abstract Background Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JIA is less studied. Polarization highly influences monocytes’ and macrophages’ effector functions, broadly separated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Here, we set out to investigate the polarization pattern and functional aspects of synovial monocytes in oligoarticular juvenile idiopathic arthritis (JIA). Methods Paired synovial fluid, blood samples (n = 13) and synovial biopsies (n = 3) were collected from patients with untreated oligoarticular JIA. Monocytes were analyzed for polarization markers by flow cytometry and qPCR. Effector function was analyzed by a phagocytosis assay. Polarization of healthy monocytes was investigated by stimulation with synovial fluid in vitro. Monocyte/macrophage distribution, polarization and mRNA expression were investigated in biopsies by immunohistochemistry, immunofluorescence and in situ hybridization. Results Children with oligoarticular JIA have polarized synovial fluid monocytes of a specific M1(IFNg)/M2(IL-4)-like pattern. This was evidenced by increased surface expression of CD40 (p < 0.001), CD86 (p < 0.001) and CD206 (p < 0.001), but not CD163, as compared to paired circulating monocytes, and extensively explored at the mRNA level were synovial fluid monocytes differentially expressed classical markers of M1(IFNg)/M2(IL-4) polarization. Synovial fluid monocytes were functionally affected, as assessed by reduced capacity to phagocytose (p < 0.01). Synovial fluid induced M2 (CD16 and CD206), but not M1 (CD40 and CD86) markers in healthy monocytes and did not induce cytokine production. Single and co-expression of surface CD40 and CD206, as well as mRNA expression of IL-10 and TNF, was observed in monocytes/macrophages in synovial biopsies. Conclusion Children with untreated oligoarticular JIA have similar and distinct synovial fluid monocyte polarization pattern of mixed pro- and anti-inflammatory features. This pattern was not exclusively a result of the synovial fluid milieu as monocytes/macrophages in the synovial membrane show similar patterns. Our study highlights a distinct polarization pattern in oligoarticular JIA, which could be utilized for future treatment strategies.

scholarly journals Apple Flavonols Mitigate Adipocyte Inflammation and Promote Angiogenic Factors in LPS- and Cobalt Chloride-Stimulated Adipocytes, in Part by a Peroxisome Proliferator-Activated Receptor-γ-Dependent Mechanism

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1386 ◽  
Author(s):  
Danyelle M. Liddle ◽  
Meaghan E. Kavanagh ◽  
Amanda J. Wright ◽  
Lindsay E. Robinson
Keyword(s):  
Mrna Expression ◽  
Cobalt Chloride ◽  
Nuclear Factor Κb ◽  
Diglycidyl Ether ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Anti Inflammatory

Adipose tissue (AT) expansion induces local hypoxia, a key contributor to the chronic low-grade inflammation that drives obesity-associated disease. Apple flavonols phloretin (PT) and phlorizin (PZ) are suggested anti-inflammatory molecules but their effectiveness in obese AT is inadequately understood. Using in vitro models designed to reproduce the obese AT microenvironment, 3T3-L1 adipocytes were cultured for 24 h with PT or PZ (100 μM) concurrent with the inflammatory stimulus lipopolysaccharide (LPS; 10 ng/mL) and/or the hypoxia mimetic cobalt chloride (CoCl2; 100 μM). Within each condition, PT was more potent than PZ and its effects were partially mediated by peroxisome proliferator-activated receptor (PPAR)-γ (p < 0.05), as tested using the PPAR-γ antagonist bisphenol A diglycidyl ether (BADGE). In LPS-, CoCl2-, or LPS + CoCl2-stimulated adipocytes, PT reduced mRNA expression and/or secreted protein levels of inflammatory and macrophage chemotactic adipokines, and increased that of anti-inflammatory and angiogenic adipokines, which was consistent with reduced mRNA expression of M1 polarization markers and increased M2 markers in RAW 264.7 macrophages cultured in media collected from LPS + CoCl2-simulated adipocytes (p < 0.05). Further, within LPS + CoCl2-stimulated adipocytes, PT reduced reactive oxygen species accumulation, nuclear factor-κB activation, and apoptotic protein expression (p < 0.05). Overall, apple flavonols attenuate critical aspects of the obese AT phenotype.

scholarly journals Gastric leptin, but not estrogen and somatostatin, contributes to the elevation of ghrelin mRNA expression level in fasted rats

2007 ◽  
Vol 196 (3) ◽  
pp. 529-538 ◽  
Author(s):  
Zheng Zhao ◽  
Ichiro Sakata ◽  
Yusuke Okubo ◽  
Kanako Koike ◽  
Kenji Kangawa ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Leptin Receptor ◽  
Mrna Level ◽  
Expression Level ◽  
Male Rats ◽  
Pcr Analysis ◽  
Fasting State ◽  
Ghrelin Secretion ◽  
Fasted Rats

Ghrelin, an endogenous ligand for the GH secretagog receptor, is predominantly produced in the stomach. It has been reported that endogenous ghrelin levels are increased by fasting and decreased after refeeding. It has also been reported that estrogen upregulates ghrelin expression and production and that somatostatin inhibits ghrelin secretion, whereas leptin has a paradoxical effect. Recently, several studies have shown that estrogen, somatostatin, and leptin are produced in the stomach, but the direct effects of these gastric hormones on ghrelin expression in a fasting state remain obscure. In this study, we examined the mRNA expression levels of gastric ghrelin, aromatase (estrogen synthetase), leptin and somatostatin, and concentrations of stomach leptin and portal vein 17β-estradiol in fasted male rats. After 48 h of fasting, although gastric ghrelin mRNA level was significantly increased, both gastric leptin mRNA level and leptin content were decreased. Further, refeeding of fasted rats resulted in a decrease in ghrelin expression level and an increase in leptin expression level. On the other hand, gastric estrogen and somatostatin levels did not change after fasting. In vitro studies revealed that leptin dose-dependently inhibited ghrelin expression and also inhibited estrogen-stimulated ghrelin expression. Moreover, ghrelin cells were found to be tightly surrounded by leptin cells. RT-PCR analysis clearly showed that long and short forms of the leptin receptor are expressed in the rat stomach. These results strongly suggest that an elevated gastric ghrelin expression level in a fasting state is regulated by attenuated restraint from decreased gastric leptin level.

scholarly journals Synovial Fluid Neutrophils in Oligoarticular Juvenile Idiopathic Arthritis Have an Altered Phenotype and Impaired Effector Functions

2021 ◽  
Author(s):  
Sabine Arve-Butler ◽  
Tobias Schmidt ◽  
Anki Mossberg ◽  
Elisabet Berthold ◽  
Birgitta Gullstrand ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Oxidative Burst ◽  
Joint Inflammation ◽  
Mannose Receptor ◽  
Inactive Disease ◽  
Phagocytic Capacity ◽  
Effector Functions ◽  
Oligoarticular Juvenile Idiopathic Arthritis ◽  
And Function

Abstract BackgroundNeutrophils are the most prevalent immune cells in synovial fluid in inflamed joints of children with oligoarticular juvenile idiopathic arthritis (JIA). Despite this, little is known about neutrophil function at the site of inflammation in JIA and how local neutrophils contribute to disease pathogenesis. This study aimed to characterize phenotype and function of synovial fluid neutrophils in oligoarticular JIA.Methods Neutrophils obtained from paired blood and synovial fluid from patients with active oligoarticular JIA were investigated phenotypically (n=17) and functionally (phagocytosis and oxidative burst, n=13) by flow cytometry. In a subset of patients (n=6), blood samples were also obtained during inactive disease at a follow-up visit. Presence of CD206-expressing neutrophils was investigated in synovial biopsies from four patients by immunofluorescence. ResultsNeutrophils in synovial fluid had an activated phenotype, characterized by increased CD66b and CD11b levels, and most neutrophils had a CD16hi CD62Llow aged phenotype. A large proportion of the synovial fluid neutrophils expressed CD206, a mannose receptor not commonly expressed by neutrophils but by monocytes, macrophages and dendritic cells. CD206 expressing neutrophils were also found in synovial tissue biopsies. The synovial fluid neutrophil phenotype was not dependent on transmigration alone. Functionally, synovial fluid neutrophils had reduced phagocytic capacity and a trend towards impaired oxidative burst compared to blood neutrophils. In addition, the effector functions of the synovial fluid neutrophils correlated negatively with the proportion of CD206+ neutrophils.ConclusionsNeutrophils in the inflamed joint in oligoarticular JIA were altered, both regarding phenotype and function. Neutrophils in the synovial fluid were activated, had an aged phenotype, had gained monocyte-like features and had impaired phagocytic capacity. The impairment in phagocytosis and oxidative burst was associated to the phenotype shift. We speculate that these neutrophil alterations might play a role in the sustained joint inflammation seen in JIA.

scholarly journals The Potential Anti-Inflammatory Effects of Brucea javanica (L.) Merr.

2021 ◽  
Vol 6 (9) ◽  
pp. 1-7
Author(s):  
Sisi Mustika ◽  
Sri Oktavia ◽  
Ifora Ifora
Keyword(s):  
Mrna Expression ◽  
Initial Response ◽  
In Vivo Studies ◽  
Brucea Javanica ◽  
Ppar Γ ◽  
Pharmacological Studies ◽  
Ifn Γ ◽  
Anti Inflammatory

Inflammation is the initial response to acute and chronic tissue damage, which is characterized by redness, swelling, heat, and pain. Natural products derived from plants have specific pharmacological activity and minimal side effects. Brucea javanica is a plant that has an anti-inflammatory effect, this plant contains alkaloid and flavonoid compounds. Flavonoids have the ability to block cyclooxygenase and lipoxygenase while alkaloids as an anti-inflammatory are thought to work by inhibiting prostaglandin H2 PGH2 which is an inflammatory mediator. From the data obtained, there is no complete literature that reviews its use as an anti-inflammatory. The search databases used are as follows: Pubmed, ScienceDirect, and Google Scholar to study the anti-inflammatory activity of Brucea javanica. All recent research articles were published between 2010 to 2021. Based on eligibility, 4 studies were included in this study, consisting of 2 In vivo studies and 2 In vitro and In vivo studies. A series of pharmacological studies have reported that Brucea javanica can block the Nf-kB signaling pathway and decrease the production of inflammatory mediators. It has been reported to be able to inhibit the production of NO, PGE2, TNF-, IL-1β, IL-18IL-23, COX-2, NF-κB, IFN-γ, IL-6, the levels of MPO (Myeloperoxidase), reducing the edema and induce the production of the anti-inflammatory cytokine (IL-4, IL-10 and TGF-β). Brucea javanica also markedly activates Nrf2 expression suppressing the inflammatory response-mediated NLRP3 and NF-κB activation. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE was remarkably inhibited by Brucea javanica, while the mRNA expression of PPAR-γ was significantly enhanced. In vitro and in vivo studies strongly indicate that Brucea javanica has the potential as an anti-inflammatory.

scholarly journals Anti-periodontal Pathogen and Anti-inflammatory Activities of Oxyresveratrol

2013 ◽  
Vol 8 (5) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Waranyoo Phoolcharoen ◽  
Sireerat Sooampon ◽  
Boonchoo Sritularak ◽  
Kittisak Likhitwitayawuid ◽  
Jintakorn Kuvatanasuchati ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Pathogenic Bacteria ◽  
Biological Activities ◽  
Mrna Level ◽  
Periodontal Pathogen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Minimal Bactericidal Concentration ◽  
Potential Candidate ◽  
Anti Inflammatory

Oxyresveratrol, a compound in the heartwood of Artocarpus lakoocha Roxb and other medicinal plants, has been shown to have various biological activities. However, these have not been studied in periodontal research. In this study, we investigated whether oxyresveratrol has antibacterial activity against the predominant perio-pathogenic bacteria Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Moreover, the anti-inflammatory properties of oxyresveratrol were studied in LPS-stimulated human periodontal ligament (hPDL) cells. The antibacterial activity of oxyresveratrol on P. gingivalis and A. actinomycetemcomitans was initially evaluated using a disc diffusion test. The anti-bacterial strength of oxyresveratrol was then assessed in vitro by determining the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC). Furthermore, the effects of oxyresveratrol on the LPS-induced production of inflammatory mediators were measured in hPDL cells. The levels of cytokine mRNA and protein expression were determined using reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that oxyresveratrol exhibited antibacterial activities against P. gingivalis with MIC and MBC values of 0.07 mg/mL and 0.16 mg/mL, respectively. The MIC and MBC values against A. actinomycetemcomitans were 0.08 mg/mL and 0.16 mg/mL, respectively. When examining inflammatory stimulation, LPS treatment strongly induced the expression of pro-inflammatory cytokines in hPDL cells. However, pre-treatment with oxyresveratrol significantly inhibited the expression of IL-6 and IL-8 at both the mRNA and protein levels. The IL-1β mRNA level was suppressed by oxyresveratrol, but the level of secreted IL-1β protein was not detectable using ELISA. The results of the present study indicate that oxyresveratrol is a potential candidate for use as an anti-periodontitis agent because of its anti-bacterial activity against the main oral pathogens related to periodontal disease and its anti-inflammatory activity in LPS-stimulated hPDL cells.

scholarly journals Curcumin Attenuates Environment-Derived Osteoarthritis by Sox9/NF-kB Signaling Axis

2021 ◽  
Vol 22 (14) ◽  
pp. 7645
Author(s):  
Constanze Buhrmann ◽  
Aranka Brockmueller ◽  
Anna-Lena Mueller ◽  
Parviz Shayan ◽  
Mehdi Shakibaei
Keyword(s):  
Inflammatory Responses ◽  
Curcuma Longa ◽  
Mrna Level ◽  
Chondrocyte Apoptosis ◽  
Chondrocyte Viability ◽  
Tnf Α ◽  
Signaling Axis ◽  
Collagen Ii ◽  
Anti Inflammatory

Inflammation has a fundamental impact on the pathophysiology of osteoarthritis (OA), a common form of degenerative arthritis. It has previously been established that curcumin, a component of turmeric (Curcuma longa), has anti-inflammatory properties. This research evaluates the potentials of curcumin on the pathophysiology of OA in vitro. To explore the anti-inflammatory efficacy of curcumin in an inflamed joint, an osteoarthritic environment (OA-EN) model consisting of fibroblasts, T-lymphocytes, 3D-chondrocytes is constructed and co-incubated with TNF-α, antisense oligonucleotides targeting NF-kB (ASO-NF-kB), or an IkB-kinase (IKK) inhibitor (BMS-345541). Our results show that OA-EN, similar to TNF-α, suppresses chondrocyte viability, which is accompanied by a significant decrease in cartilage-specific proteins (collagen II, CSPG, Sox9) and an increase in NF-kB-driven gene proteins participating in inflammation, apoptosis, and breakdown (NF-kB, MMP-9, Cox-2, Caspase-3). Conversely, similar to knockdown of NF-kB at the mRNA level or at the IKK level, curcumin suppresses NF-kB activation, NF-kB-promotes gene proteins derived from the OA-EN, and stimulates collagen II, CSPG, and Sox9 expression. Furthermore, co-immunoprecipitation assay shows that curcumin reduces OA-EN-mediated inflammation and chondrocyte apoptosis, with concomitant chondroprotective effects, due to modulation of Sox-9/NF-kB signaling axis. Finally, curcumin selectively hinders the interaction of p-NF-kB-p65 directly with DNA—this association is disrupted through DTT. These results suggest that curcumin suppresses inflammation in OA-EN via modulating NF-kB-Sox9 coupling and is essential for maintaining homeostasis in OA by balancing chondrocyte survival and inflammatory responses. This may contribute to the alternative treatment of OA with respect to the efficacy of curcumin.

scholarly journals Euryops arabicus Promotes Healing of Excised Wounds in Rat Skin: Emphasis on Its Collagen-Enhancing, Antioxidant, and Anti-Inflammatory Activities

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Ahmed Abdel-Lateff ◽  
Ashraf B. Abdel-Naim ◽  
Walied M. Alarif ◽  
Mardi M. Algandaby ◽  
Najla A. Alburae ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Folk Medicine ◽  
Antioxidant Properties ◽  
Skin Wound ◽  
Tnf Α ◽  
The Family ◽  
Anti Inflammatory ◽  
Tgf Β1

Euryops arabicus Steud (E. arabicus) belongs to the family Asteraceae. It has several uses in folk medicine in the Arabian Peninsula. The current study aimed at evaluating the wound healing properties of the E. arabicus extract in rats. Primarily, E. arabicus successfully accelerated cell migration in vitro and it also showed no signs of dermal toxicity. Topical application of E. arabicus extract (5% or 20%) expedited healing of excised skin in rats. Histological examinations indicated that E. arabicus shortened epithelization period, stimulated fibroblast activity, and increased collagen deposition in wound tissues. The plant extract exerted antioxidant activity as evidenced by inhibition of GSH depletion and MDA accumulation and enhanced mRNA expression of Sod1 in wound tissues collected at the end of the experiment. Further, E. arabicus inhibited the rise of TNF-α and IL-1β in the skin wound region. The anti-inflammatory was confirmed by the observed down regulation of Ptgs2, Nos2, IL-6, and NF-κB mRNA expression. In addition, the extract enhanced the expression of TGF-β1 and HIF-1α in wounded skin tissues as indicated immunohistochemically. Conclusively, E. arabicus expedites excision wound healing in rats. Collagen-enhancing, anti-inflammatory, and antioxidant properties mediate the observed wound healing activity. These findings might contribute to our understanding of the ethnobotanical use of E. arabicus in wounds.

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