scholarly journals The Effects of the Molecular Weights of Hyaluronic Acid on the Immune Responses

2021 ◽  
Author(s):  
Bo Mi Lee ◽  
Sang Jun Park ◽  
Insup Noh ◽  
Chun-Ho Kim
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
Inflammatory Responses ◽  
No Production ◽  
Rt Pcr ◽  
High Concentration ◽  
Molecular Weights ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Tgf Β1

Abstract Background: The molecular weight of hyaluronic acid (HyA) depends on the type of organ in the body. When HyA of the desired molecular weight is implanted into the human body for regeneration of damaged tissue, it is degraded by hyaluronidase in associated with an inflammatory response. This study sought to evaluate the effects of HyA molecular weight and concentration on pro- and anti-inflammatory responses in murine macrophages. Methods: The structures and molecular weights of HyAs (LMW-10, MMW-100, MMW-500, and HMW-1,500) were confirmed by 1H NMR and gel permeation chromatography (GPC), respectively. After treatment of murine macrophages with a low (100 μg/mL) or high (100 μg/mL) concentration of each molecular weight HyA, cells were stimulated with lipopolysaccharide (LPS) and changes in immune response in both LPS-stimulated and untreated macrophages were evaluated by assessing nitric oxide (NO) production, and analyzing expression of pro- and anti-inflammatory genes including by RT-PCR.Results: Molecular weights of LMW-10, MMW-100, MMW-500, and HMW-1,500 were 13,241±161, 96,531±1,167, 512,657±8,545, and 1,249,500±37,477 Da, respectively. NO production by LPS-stimulated macrophages was decreased by increasing concentrations and molecular weights of HyA. At a high concentration of 100 μg/mL, HMW-1,500 reduced NO production in LPS-stimulated macrophages to about 45%. Using NanoString technology, we also found that the immune-related genes TNF‐α, IL-6, IL-1β, TGF-β1, IL-10, IL-11, CCL2, and Arg1 were specifically over-expressed in LPS-stimulated macrophages treated with various molecular weights of HyA. An RT-PCR analysis of gene expression showed that HMW-1,500 decreased expression of classically activated (M1) macrophage genes, such as TNF‐α, IL-6, CCL2, and IL-1β, in LPS-stimulated macrophages, whereas medium molecular-weight HyA (MMW-100 and MMW-500) instead increased expression levels of these genes. HMW-1,500 at a high concentration (100 μg/mL) significantly decreased expression of pro-inflammatory genes in LPS-stimulated macrophages. Expression of genes associated with anti-inflammatory responses (M2 phenotype), such as TGF-β1, IL-10, IL-11, and Arg1, were increased by high concentrations of MMW-500 and HMW-1,500 in LPS-stimulated macrophages.Conclusions: High molecular-weight HyA (i.e., > 1,250 kDa) inhibits pro-inflammatory responses in LPS-stimulated macrophages and induces anti-inflammatory responses in a concentration dependent manner.

scholarly journals The effects of the molecular weights of hyaluronic acid on the immune responses

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Bo Mi Lee ◽  
Sang Jun Park ◽  
Insup Noh ◽  
Chun-Ho Kim
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
Inflammatory Responses ◽  
No Production ◽  
Rt Pcr ◽  
High Concentration ◽  
Molecular Weights ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Tgf Β1

Abstract Background The molecular weight of hyaluronic acid (HyA) depends on the type of organ in the body. When HyA of the desired molecular weight is implanted into the human body for regeneration of damaged tissue, it is degraded by hyaluronidase in associated with an inflammatory response. This study sought to evaluate the effects of HyA molecular weight and concentration on pro- and anti-inflammatory responses in murine macrophages. Methods The structures and molecular weights of HyAs (LMW-10, MMW-100, MMW-500, and HMW-1,500) were confirmed by 1 H NMR and gel permeation chromatography (GPC), respectively. After treatment of murine macrophages with a low (10 µg/mL) or high (100 µg/mL) concentration of each molecular weight HyA, cells were stimulated with lipopolysaccharide (LPS) and changes in immune response in both LPS-stimulated and untreated macrophages were evaluated by assessing nitric oxide (NO) production, and analyzing expression of pro- and anti-inflammatory genes including by RT-PCR. Results Molecular weights of LMW-10, MMW-100, MMW-500, and HMW-1,500 were 13,241 ± 161, 96,531 ± 1,167, 512,657 ± 8,545, and 1,249,500 ± 37,477 Da, respectively. NO production by LPS-stimulated macrophages was decreased by increasing concentrations and molecular weights of HyA. At a high concentration of 100 µg/mL, HMW-1,500 reduced NO production in LPS-stimulated macrophages to about 45 %. Using NanoString technology, we also found that the immune-related genes TNF-α, IL-6, IL-1β, TGF-β1, IL-10, IL-11, CCL2, and Arg1 were specifically over-expressed in LPS-stimulated macrophages treated with various molecular weights of HyA. An RT-PCR analysis of gene expression showed that HMW-1,500 decreased expression of classically activated (M1) macrophage genes, such as TNF‐α, IL-6, CCL2, and IL-1β, in LPS-stimulated macrophages, whereas medium molecular-weight HyA (MMW-100 and MMW-500) instead increased expression levels of these genes. HMW-1,500 at a high concentration (100 µg/mL) significantly decreased expression of pro-inflammatory genes in LPS-stimulated macrophages. Expression of genes associated with anti-inflammatory responses (M2 phenotype), such as TGF-β1, IL-10, IL-11, and Arg1, were increased by high concentrations of MMW-500 and HMW-1,500 in LPS-stimulated macrophages. Conclusions High molecular-weight HyA (i.e., > 1,250 kDa) inhibits pro-inflammatory responses in LPS-stimulated macrophages and induces anti-inflammatory responses in a concentration dependent manner.

scholarly journals Phytosterols Suppress Phagocytosis and Inhibit Inflammatory Mediators via ERK Pathway on LPS-Triggered Inflammatory Responses in RAW264.7 Macrophages and the Correlation with Their Structure

Foods ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 582 ◽  
Author(s):  
Yuan ◽  
Zhang ◽  
Shen ◽  
Jia ◽  
Xie
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Ester Group ◽  
No Production ◽  
Raw264.7 Macrophages ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase

Phytosterols, found in many commonly consumed foods, exhibit a broad range of physiological activities including anti-inflammatory effects. In this study, the anti-inflammatory effects of ergosterol, β-sitosterol, stigmasterol, campesterol, and ergosterol acetate were investigated in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Results showed that all phytosterol compounds alleviated the inflammatory reaction in LPS-induced macrophage models; cell phagocytosis, nitric oxide (NO) production, release of tumor necrosis factor-α (TNF-α), and expression and activity of pro-inflammatory mediator cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and phosphorylated extracellular signal-regulated protein kinase (p-ERK) were all inhibited. The anti-inflammatory activity of β-sitosterol was higher than stigmasterol and campesterol, which suggests that phytosterols without a double bond on C-22 and with ethyl on C-24 were more effective. However, inconsistent results were observed upon comparison of ergosterol and ergosterol acetate (hydroxy or ester group on C-3), which suggest that additional research is still needed to ascertain the contribution of structure to their anti-inflammatory effects.

scholarly journals Combined Administration of Recombinant TGF-β1 and DMSO Decreases the in Vitro Inflammatory Properties of Neutrophils from Sickle Cell Anemia Individuals

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2366-2366
Author(s):  
Lidiane S. Torres ◽  
Lediana I. Miguel ◽  
Merav E. Shaul ◽  
Zvi G. Fridlender ◽  
Wilson A. Ferreira ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Conflicts Of Interest ◽  
Combined Treatment ◽  
Inflammatory Stress ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Tgf Β1

Abstract Sickle cell anemia (SCA) is a chronic inflammatory disease, in which activated neutrophils play a role in initiating vaso-occlusion. Two populations of circulating neutrophils have been described, denominated as low-(LDN) and high-(HDN) density neutrophils. Circulating numbers of LDN (a less inflammatory subset) are normally minimal, but this population augments under inflammatory stress, such as that seen in cancer. Transforming growth factor beta-1 (TGF-β1) is a cytokine with anti-inflammatory properties that is elevated in SCA. In conditions such as Chron's disease, TGF-β1 has protective effects, mediated by its immuno-suppressive functions. In macrophages, it is thought to trigger the polarization from pro- (M1) to anti-inflammatory phenotypes (M2), which hypothetically occur in neutrophils too (N1 and N2). Moreover, dimethyl sulfoxide (DMSO) reportedly increases TGF-β receptors expression on epithelial cells. We aimed to characterize the subsets of circulating neutrophils in SCA patients and investigate the effects of TGF-β1 and DMSO on these cells. Neutrophils from healthy (CON) and SCA individuals, in steady state and without blood transfusion for 90 days, were isolated from peripheral blood by Ficoll-Paque density gradient centrifugation. HDN and LDN were obtained from the granulocyte and mononuclear layers, respectively, and stained with CD66b for neutrophil identification by flow cytometry. As no significant effect of hydroxyurea (HU) therapy on the data obtained was observed, patients' data were grouped together irrespective of HU use. Percentages of LDN were calculated based on the total of gated CD66b+ cells. SCA patients had higher levels of LDN than CON (3.2±0.9%, N=7 vs 1.3±0.3%, N=13; p=0.02). We next investigated the presence of CD66b+/CD206- and CD66b+/CD206+ cells, to infer the presence of N1 and N2 phenotypes, respectively. N2 were more frequent in the LDN than in the HDN subset (CON: 68.1±3.3% vs 52.0±4.4%, N=9, p=0.01; SCA: 77.6±8.9% vs 44.1±5.0%, N=3, p=0.03). To determine whether TGF-β1 and DMSO could shift HDN to a LDN profile, cells were treated (2h) with TGF-β1 (50pM) and/or DMSO (1.5%). Treatments with DMSO alone or combined with TGF-β1 increased the percentage of CD206+ cells in CON (45.7±2.1% vs 61.9±7.6 and 53.6±2.6% respectively, N=6, p=0.04), as well as CD206+ expression on each cell (mean fluorescence intensity, MFI) (137.5±16.9 MFI vs 293.6±71.2 MFI and 210.1±23.9 MFI, respectively, p=0.03). In SCA, only the combined TGF-β1/DMSO treatment increased the MFI of CD206 in HDN (115.7±10.2 vs 255.8±29.7 MFI, N=4, p=0.03). We next investigated whether TGF-β1/DMSO could reduce the adhesion of HDN to fibronectin ligand (FN, 20μg/mL) using static adhesion assays (30 min, 37ºC). HDN from CON and SCA were treated with TGF-β1 and/or DMSO (90min) and stimulated with TNF-α (200ng/mL, 30min). Although TGF-β1 alone did not reduce the adhesion of HDN to FN (p>0.05), the addition of DMSO decreased TNF-α-induced adhesion in CON (16.5±1.8% to 11.3±1.5%, p=0.03, N=10) and SCA HDN (38.9±23.9% to 13.9±1.5%, p=0.04, N=3). Subsequently, HDN were stimulated (4h) with LPS (100ng/mL) and INF-γ (20ng/mL), to induce N2 polarization, in the presence/absence of TGF-β1 and DMSO. The combined treatment again reduced adhesion in both groups (CON: 11.1±1.5% to 4.2±1.2%, p<0.01, N=4; SCA: 47.4±12.3% vs 21.9±4.5%, p=0.04, N=4). To assess whether TGF-β1 and DMSO could affect the production of proinflammatory cytokines by HDN after stimulation with LPS/INF-γ, TNF-α and IL-1β levels in cell supernatants were measured by ELISA. TGF-β1 and DMSO, in combination, decreased both TNF-α and IL-1β release from CON (TNF-α: 39.7±8.7pg/mL to 8.7±0.9pg/mL, p<0.01, N=6; IL-1β: 66.9±10.5pg/mL to 16.5±5.1pg/mL, p=0.02, N=4) and SCA HDN (TNF-α: 174.0±55.5pg/mL to 21.8±6.6pg/mL, p=0.01, N=8; IL-1β: 103.6±25.6pg/mL to 43.1±15.5pg/mL, p=0.01, N=8). Our results demonstrate for the first time the presence of elevated numbers of LDN in SCA patients, indicating an increased basal response to inflammatory stress. However, this shift in the anti-inflammatory subset does not appear enough to control inflammatory responses in the disease, and the use of agents capable of inducing this polarization may be a promising approach. Moreover, the anti-inflammatory effects of TGF-β1 on HDN seem to be enhanced by DMSO and suggest this combination as an effective modulator of the inflammatory profile of neutrophils. Disclosures No relevant conflicts of interest to declare.

scholarly journals Rosanortriterpenes A–B, Two Promising Agents from Rosa laevigata var. leiocapus, Alleviate Inflammatory Responses and Liver Fibrosis in In Vitro Cell Models

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Bai-Lin Li ◽  
Juan-Juan Hu ◽  
Jin-Dan Xie ◽  
Chen Ni ◽  
Hui-Jun Liang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Inflammatory Responses ◽  
No Production ◽  
Western Blot Assay ◽  
Necrosis Factor Alpha ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Rosa Laevigata

Rosanortriterpenes A–B (RTA and RTB), two nortriterpenoids, are characteristic constituents in the fruits of Rosa laevigata var. leiocapus. However, pharmacological studies on these compounds are still scarce. In the present study, we aim to investigate the anti-inflammatory mechanisms associated with the effects of RTA–B in RAW264.7 macrophages and LO2 cells by detecting cell viabilities, nitric oxide (NO) production, tumour necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) production. Simultaneously, the anti-inflammatory action mechanisms of these two compounds were illustrated through western blot assay. Besides, the antihepatic fibrosis activities of these compounds have also been explored. The results demonstrated that RTA and RTB inhibited the production of NO, TNF-α, and IL-6 and suppressed liver fibrosis. RTA and RTB treatment also greatly inhibited the activation of NF-kappaB (NF-κB) pathway. Our study confirmed the promising anti-inflammatory and anti-liver fibrosis actions of RTA–B, suggesting that they might be developed as alternative and promising drugs for the treatment of hepatic inflammatory and fibrotic diseases.

scholarly journals Pirfenidone attenuates synovial fibrosis and postpones the progression of osteoarthritis by anti-fibrotic and anti-inflammatory properties in vivo and in vitro

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qilu Wei ◽  
Ning Kong ◽  
Xiaohui Liu ◽  
Run Tian ◽  
Ming Jiao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fast Green ◽  
Expression Levels ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Safranin O ◽  
Tgf Β1

Abstract Background Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown. Methods Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-β1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson’s trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading. Results The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-β1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-β1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-β1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson’s trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA. Conclusions PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.

scholarly journals Bioactivity-Guided Extract Optimization of Osmanthus fragrans var. aurantiacus Leaves and Anti-Inflammatory Activities of Phillyrin

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1545
Author(s):  
Hwa-Young Song ◽  
Da-Eun Jeong ◽  
Mina Lee
Keyword(s):  
Biological Activities ◽  
Radical Scavenging ◽  
No Production ◽  
Dependent Manner ◽  
Optimal Method ◽  
Concentration Dependent Manner ◽  
Osmanthus Fragrans ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Extracellular Regulated Kinase

The aim of this study was to identify the optimal extraction conditions for leaves of Osmanthus fragrans var. aurantiacus. Inhibitory effects of various extracts on NO production were compared. Antioxidant evaluations for total phenol and flavonoid contents were carried out using various extracts of O. fragrans var. aurantiacus leaves obtained under optimal extraction conditions that showed the greatest effect on NO production. The optimal method for extracting O. fragrans var. aurantiacus leaves resulted in an extract named OP OFLE. OP OFLE showed DPPH and ABTS radical scavenging activities in a concentration-dependent manner. Phillyrin (PH) was isolated as a major compound from OP OFLE by HPLC/DAD analysis. OP OFLE and PH reduced inducible nitric oxide (iNOS) and cyclooxygenase (COX)-2 protein expression and downregulated proinflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 and HT-29 cells. To determine the signal pathway involved in the inhibition of NO production, a Western blot analysis was performed. Results showed that OP OFLE decreased phosphorylation of extracellular regulated kinase (pERK) 1/2 and the expression of nuclear factor-kappa B (NF-κB). Our results suggest that extracts of O. fragrans var. aurantiacus leaves and its major components have biological activities such as antioxidative and anti-inflammatory properties.

scholarly journals From Inflammation to the Onset of Fibrosis through A2A Receptors in Kidneys from Deceased Donors

2020 ◽  
Vol 21 (22) ◽  
pp. 8826
Author(s):  
Elena Guillén-Gómez ◽  
Irene Silva ◽  
Núria Serra ◽  
Francisco Caballero ◽  
Jesús Leal ◽  
...  
Keyword(s):  
Deceased Donor ◽  
Inflammatory Factors ◽  
Mrna Levels ◽  
A2a Adenosine Receptor ◽  
A2a Receptors ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pka Pathway ◽  
Tgf Β1 ◽  
M2 Phenotype

Pretransplant graft inflammation could be involved in the worse prognosis of deceased donor (DD) kidney transplants. A2A adenosine receptor (A2AR) can stimulate anti-inflammatory M2 macrophages, leading to fibrosis if injury and inflammation persist. Pre-implantation biopsies of kidney donors (47 DD and 21 living donors (LD)) were used to analyze expression levels and activated intracellular pathways related to inflammatory and pro-fibrotic processes. A2AR expression and PKA pathway were enhanced in DD kidneys. A2AR gene expression correlated with TGF-β1 and other profibrotic markers, as well as CD163, C/EBPβ, and Col1A1, which are highly expressed in DD kidneys. TNF-α mRNA levels correlated with profibrotic and anti-inflammatory factors such as TGF-β1 and A2AR. Experiments with THP-1 cells point to the involvement of the TNF-α/NF-κB pathway in the up-regulation of A2AR, which induces the M2 phenotype increasing CD163 and TGF-β1 expression. In DD kidneys, the TNF-α/NF-κB pathway could be involved in the increase of A2AR expression, which would activate the PKA–CREB axis, inducing the macrophage M2 phenotype, TGF-β1 production, and ultimately, fibrosis. Thus, in inflamed DD kidneys, an increase in A2AR expression is associated with the onset of fibrosis, which may contribute to graft dysfunction and prognostic differences between DD and LD transplants.

scholarly journals Hyaluronic Acid-Modified and TPCA-1-Loaded Gold Nanocages Alleviate Inflammation

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 143 ◽  
Author(s):  
Jingnan Zhao
Keyword(s):  
Hyaluronic Acid ◽  
Inflammatory Cells ◽  
Oxygen Species ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Nanogold Particles ◽  
Gold Nanocages ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Gold nanocages (AuNCs) are biocompatible and porous nanogold particles that have been widely used in biomedical fields. In this study, hyaluronic acid (HA) and peptide- modified gold nanocages (HA-AuNCs/T/P) loaded with 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) were prepared to investigate their potential for combating inflammation. TPCA-1 was released from AuNCs, intracellularly when HA was hydrolyzed by hyaluronidase. HA-AuNCs/T/P show a much higher intracellular uptake than AuNCs/T/P, and exhibit a much higher efficacy on the suppression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) than free TPCA-1, suggesting great improvement to the anti-inflammatory efficacy of TPCA-1 through the application of AuNCs. HA-AuNCs/T/P can also reduce the production of reactive oxygen species in inflammatory cells. This study suggests that HA-AuNCs/T/P may be potential agents for anti-inflammatory treatment, and are worthy of further investigation.

scholarly journals In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Gene Expressions ◽  
Tnf Α ◽  
Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

scholarly journals Anti-inflammatory and Matrix Metallopeptidase-1-Inhibitory Effects of the Cassia obtusifolia L. Seed Extract on Particulate Matter-induced Skin

2021 ◽  
Vol 19 (3) ◽  
pp. 355-363
Author(s):  
Jung-Wook Kang ◽  
In-Chul Lee
Keyword(s):  
Particulate Matter ◽  
Seed Extract ◽  
Enzyme Linked Immunosorbent Assay ◽  
No Production ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Cassia Obtusifolia ◽  
Tnf Α ◽  
Matrix Metallopeptidase ◽  
Anti Inflammatory

Purpose: This study aimed to investigate the effects of the Cassia obtusifolia L. seed extract (CSE) on particulate matter (PM)-induced skin.Methods: The effects of CSE on cell viability were evaluated using a skin cell line. To determine the anti-inflammatory effects and matrix metallopeptidase-1 (MMP-1)-inhibitory effects of CSE on PM-induced skin, NO and MMP-1 expressions were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Also, the effects of CSE was investigated the induction of IL-8 and TNF-α treated PM on reconstructed human full thickness skin models.Results: It was observed that CSE decreased NO production in PM-induced RAW 264.7 cells without cytotoxicity. In addition, CSE decreased the expression of MMP-1 in PM-induced cells in a dose-dependent manner. CSE decreased IL-8 and TNF-α production in a PM-reconstructed human skin model.Conclusion: These results indicate that CSE could be used as a cosmetic material to induce anti-inflammation and inhibition of MMP-1 in PM-induced skin.

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