Eotaxin-1/CCL11 is involved in cell migration in rheumatoid arthritis

Abstract Background: Reactive oxygen species (ROS) regulate the migration and invasion of fibroblast-like synoviocytes (FLS), which are key effector cells in rheumatoid arthritis (RA) pathogenesis. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) induces ROS generation and consequently, enhances cell migration. Despite the important interrelationship between RA, FLS, and ROS, the effect of NOX4 on RA pathogenesis remains unclear. Methods: FLS isolated from RA (n=5) and osteoarthritis (OA, n=5) patients were stimulated with recombinant interleukin 17 (IL-17; 10 ng/ml) and tumor necrosis factor alpha (TNF-α; 10 ng/ml) for 1 h. Cell migration, invasion, adhesion molecule expression, vascular endothelial growth factor (VEGF) secretion, and ROS expression were examined. The mRNA and protein levels of NOX4 were analyzed by RT-qPCR and western blotting, respectively. The NOX4 inhibitor GLX351322 and NOX4 siRNA were used to inhibit NOX4 to probe the effect of NOX4 on these cellular processes. Results: Migration of RA FLS was increased 2.48-fold after stimulation with IL-17 and TNF-α, while no difference was observed for OA FLS. ROS expression increased in parallel with invasiveness of FLS following cytokine stimulation. When the expression of NOX was examined, NOX4 was significantly increased by 9.73-fold in RA FLS compared to unstimulated FLS. Following NOX4 inhibition, cytokine-induced vascular cell adhesion molecule 1 (VCAM1), VEGF, and migration and invasion capacity of RA FLS were markedly decreased to unstimulated levels. Conclusion: NOX4 is a key contributor to cytokine-enhanced migration and invasion via modulation of ROS, VCAM1, and VEGF in RA FLS.

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The effect of nicotinamide adenine dinucleotide phosphate oxidase 4 on migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis

10.21203/rs.2.20756/v3 ◽

2020 ◽

Author(s):

Ha-Reum Lee ◽

Su-Jin Yoo ◽

Jinhyun Kim ◽

In Seol Yoo ◽

Chan Keol Park ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cell Migration ◽

Adhesion Molecule ◽

Nicotinamide Adenine Dinucleotide ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Nicotinamide Adenine ◽

Migration And Invasion ◽

Interleukin 17 ◽

Tnf Α ◽

Fibroblast Like Synoviocytes

Abstract Background: Reactive oxygen species (ROS) regulate the migration and invasion of fibroblast-like synoviocytes (FLS), which are key effector cells in rheumatoid arthritis (RA) pathogenesis. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) induces ROS generation and consequently, enhances cell migration. Despite the important interrelationship between RA, FLS, and ROS, the effect of NOX4 on RA pathogenesis remains unclear.Methods: FLS isolated from RA (n=5) and osteoarthritis (OA, n=5) patients were stimulated with recombinant interleukin 17 (IL-17; 10 ng/ml) and tumor necrosis factor alpha (TNF-α; 10 ng/ml) for 1 h. Cell migration, invasion, adhesion molecule expression, vascular endothelial growth factor (VEGF) secretion, and ROS expression were examined. The mRNA and protein levels of NOX4 were analyzed by RT-qPCR and western blotting, respectively. The NOX4 inhibitor GLX351322 and NOX4 siRNA were used to inhibit NOX4 to probe the effect of NOX4 on these cellular processes.Results: Migration of RA FLS was increased 2.48-fold after stimulation with IL-17 and TNF-α, while no difference was observed for OA FLS. ROS expression increased in parallel with invasiveness of FLS following cytokine stimulation. When the expression of NOX was examined, NOX4 was significantly increased by 9.73-fold in RA FLS compared to unstimulated FLS. Following NOX4 inhibition, cytokine-induced vascular cell adhesion molecule 1 (VCAM1), VEGF, and migration and invasion capacity of RA FLS were markedly decreased to unstimulated levels.Conclusion: NOX4 is a key contributor to cytokine-enhanced migration and invasion via modulation of ROS, VCAM1, and VEGF in RA FLS.

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The effect of nicotinamide adenine dinucleotide phosphate oxidase 4 on migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis

10.21203/rs.2.20756/v1 ◽

2020 ◽

Author(s):

Ha-Reum Lee ◽

Su-Jin Yoo ◽

Jinhyun Kim ◽

In Seol Yoo ◽

Chan Keol Park ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cell Migration ◽

Adhesion Molecule ◽

Nicotinamide Adenine Dinucleotide ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Nicotinamide Adenine ◽

Migration And Invasion ◽

Interleukin 17 ◽

Tnf Α ◽

Fibroblast Like Synoviocytes

Abstract Background: Reactive oxygen species (ROS) regulate the migration and invasion of fibroblast-like synoviocytes (FLS), which are key effector cells in rheumatoid arthritis (RA) pathogenesis. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) induces ROS generation and consequently, enhances cell migration. Despite the important interrelationship between RA, FLS, and ROS, the effect of NOX4 on RA pathogenesis remains unclear. Methods: FLS isolated from RA (n=5) and osteoarthritis (OA, n=5) patients were stimulated with recombinant interleukin 17 (IL-17; 10 ng/ml) and tumor necrosis factor alpha (TNF-α; 10 ng/ml) for 1 h. Cell migration, invasion, adhesion molecule expression, vascular endothelial growth factor (VEGF) secretion, and ROS expression were examined. The mRNA and protein levels of NOX4 were analyzed by RT-qPCR and western blotting, respectively. The NOX4 inhibitor GLX351322 and NOX4 siRNA were used to inhibit NOX4 to probe the effect of NOX4 on these cellular processes. Results: Migration of RA FLS was increased 2.48-fold after stimulation with IL-17 and TNF-α, while no difference was observed for OA FLS. ROS expression increased in parallel with invasiveness of FLS following cytokine stimulation. When the expression of NOX was examined, NOX4 was significantly increased by 9.73-fold in RA FLS compared to unstimulated FLS. Following NOX4 inhibition, cytokine-induced vascular cell adhesion molecule 1 (VCAM1), VEGF, and migration and invasion capacity of RA FLS were markedly decreased to unstimulated levels. Conclusion: NOX4 is a key contributor to cytokine-enhanced migration and invasion via modulation of ROS, VCAM1, and VEGF in RA FLS.

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MiRNA-6089 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and induces apoptosis by targeting CCR4

10.21203/rs.3.rs-20663/v1 ◽

2020 ◽

Author(s):

Suxian Lin ◽

Zhiyong Zhang ◽

Shengnan Wang ◽

Yang Lu ◽

Meilv Yang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Protein Expression ◽

Caspase 3 ◽

Healthy Controls ◽

Quantitative Real Time Pcr ◽

Qrt Pcr ◽

Tnf Α ◽

Proliferation And Apoptosis ◽

Synovial Tissues ◽

Fibroblast Like Synoviocytes

Abstract Background: Growing data have indicated that fibroblast-like synoviocytes (FLS) and miRNAs are implicated in the pathogenesis of rheumatoid arthritis (RA). This study was aimed to evaluate the function of miR-6089 in the regulation of RA-FLSs. Methods: The expression of miR-6089 was measured by quantitative real time PCR (qRT-PCR). The RA-FLSs were transfected with si-CCR4 plasmids or miR-6089 mimic, and subjected to CCK-8 and flow cytometry to analyze proliferation and apoptosis. The concentrations of MMP-1, TNF-α and IL-6 in RA-FLSs supernatant were detected using ELISA. The protein expression of caspase-3, -8 and -9 was detected using western blot.Results: The levels of miR-6089 were detected to be significantly lower in the synovial tissues and FLSs of RA than in the synovial tissues and FLSs of healthy controls. The miR-6089 up-regulation in RA-FLSs significantly inhibited the proliferation and promoted cell apoptosis accompany with an increase protein expression of caspase-3, -8 and -9. Furthermore, CCR4 was determined to directly target miR-6089, and its expression was significantly increased in the synovial tissues of RA than in the synovial tissues of healthy controls. Moreover, CCR4 overexpression effectively reversed the effect on proliferation and apoptosis induced by miR-6089 in RA-FLSs. Conclusion: Our results revealed that miR-6089 may be a potential target for RA prevention and therapy of RA.

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The effect of nicotinamide adenine dinucleotide phosphate oxidase 4 on migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis

Arthritis Research & Therapy ◽

10.1186/s13075-020-02204-0 ◽

2020 ◽

Vol 22 (1) ◽

Author(s):

Ha-Reum Lee ◽

Su-Jin Yoo ◽

Jinhyun Kim ◽

In Seol Yoo ◽

Chan Keol Park ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cell Migration ◽

Adhesion Molecule ◽

Nicotinamide Adenine Dinucleotide ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Nicotinamide Adenine ◽

Migration And Invasion ◽

Interleukin 17 ◽

Tnf Α ◽

Fibroblast Like Synoviocytes

Abstract Background Reactive oxygen species (ROS) regulate the migration and invasion of fibroblast-like synoviocytes (FLS), which are key effector cells in rheumatoid arthritis (RA) pathogenesis. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) induces ROS generation and, consequently, enhances cell migration. Despite the important interrelationship between RA, FLS, and ROS, the effect of NOX4 on RA pathogenesis remains unclear. Methods FLS isolated from RA (n = 5) and osteoarthritis (OA, n = 5) patients were stimulated with recombinant interleukin 17 (IL-17; 10 ng/ml) and tumor necrosis factor alpha (TNF-α; 10 ng/ml) for 1 h. Cell migration, invasion, adhesion molecule expression, vascular endothelial growth factor (VEGF) secretion, and ROS expression were examined. The mRNA and protein levels of NOX4 were analyzed by RT-qPCR and western blotting, respectively. The NOX4 inhibitor GLX351322 and NOX4 siRNA were used to inhibit NOX4 to probe the effect of NOX4 on these cellular processes. Results Migration of RA FLS was increased 2.48-fold after stimulation with IL-17 and TNF-α, while no difference was observed for OA FLS. ROS expression increased in parallel with invasiveness of FLS following cytokine stimulation. When the expression of NOX was examined, NOX4 was significantly increased by 9.73-fold in RA FLS compared to unstimulated FLS. Following NOX4 inhibition, cytokine-induced vascular cell adhesion molecule 1 (VCAM1), VEGF, and migration and invasion capacity of RA FLS were markedly decreased to unstimulated levels. Conclusion NOX4 is a key contributor to cytokine-enhanced migration and invasion via modulation of ROS, VCAM1, and VEGF in RA FLS.

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CD4+CD25- effector T cells from healthy controls and MS patients do not differ in mRNA expression of IFN-γ, IL-2, and TNF-α

Aktuelle Neurologie ◽

10.1055/s-2004-833325 ◽

2004 ◽

Vol 31 (S 1) ◽

Author(s):

A Hug ◽

J Haas ◽

A Viehöver ◽

B Fritz ◽

B Storch-Hagenlocher ◽

...

Keyword(s):

T Cells ◽

Mrna Expression ◽

Effector T Cells ◽

Healthy Controls ◽

Tnf Α ◽

Ifn Γ

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Penta-acetyl Geniposide Suppresses Migration, Invasion, and Inflammation of TNF-α-Stimulated Rheumatoid Arthritis Fibroblast-Like Synoviocytes Involving Wnt/β-Catenin Signaling Pathway

Inflammation ◽

10.1007/s10753-021-01495-y ◽

2021 ◽

Author(s):

Li Cai ◽

Yu-rong Mu ◽

Ming-ming Liu ◽

Meng-yuan Zhou ◽

Bo Meng ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Signaling Pathway ◽

Tnf Α ◽

Fibroblast Like Synoviocytes

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Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease

Journal of Clinical Medicine ◽

10.3390/jcm10040875 ◽

2021 ◽

Vol 10 (4) ◽

pp. 875

Author(s):

Kawaljit Kaur ◽

Shahram Vaziri ◽

Marcela Romero-Reyes ◽

Avina Paranjpe ◽

Anahid Jewett

Keyword(s):

Periodontal Disease ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Oral Disease ◽

Healthy Controls ◽

Healthy Individuals ◽

Tnf Α ◽

Blood Mononuclear Cells ◽

Ifn Γ ◽

And Function

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of peripheral blood.

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