scholarly journals RANTES and Chemotactic Activity in Synovial Fluids From Patients With Rheumatoid Arthritis and Osteoarthritis

2005 ◽  
Vol 2005 (6) ◽  
pp. 343-348 ◽  
Author(s):  
Joanna Stanczyk ◽  
Marek L. Kowalski ◽  
Janina Grzegorczyk ◽  
Barbara Szkudlinska ◽  
Marzanna Jarzebska ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Biochemical Analysis ◽  
Mononuclear Cells ◽  
Inflammatory Cells ◽  
Chemotactic Activity ◽  
Pathological Feature ◽  
Potential Mediator ◽  
Synovial Tissues ◽  
Massive Accumulation

A massive accumulation of inflammatory cells in synovial tissues is a major pathological feature of rheumatoid arthritis (RA). Neutrophiles dominate synovial fluid while rheumatoid synovium is infiltrated with mononuclear cells. Mechanisms regulating influx of particular subpopulations of leukocytes into articular cavity and synovium compartment are not completely defined. An increasing amount of data supports a crucial role of a C-C chemokine RANTES in the RA pathogenesis. Our objective is to evaluate chemotactic activity for neutrophils (NCA), lymphocytes (LCA), and monocytes (MoCA) in SFs obtained from patients with RA and osteoarthritis (OA). We also aimed to characterise the relation between chemotactic activity, RANTES, and percentage distribution of leukocytes in SF. SFs from 11 patients with RA and 6 with OA were included in the study. Modified microchamber Boyden method was employed to assess chemotactic activity. Cytological and biochemical analysis of SF was performed. RANTES was measured with ELISA. Rheumatoid SFs were rich in cells with predominance of neutrophiles while osteoarthritic fluids were lymphocytic. RA SFs were also characterised by increased lactoferrin level. Both NCA and LCA were higher in SF from patients with RA (62±12and24±6cells/HPF, resp) as compared to patients with OA (23±6;P<.05and6±2cells/HPF;P<0.05). The chemoattractive effect of RA SF was more pronounced on neutrophiles than on lymphocytes. RA SF expressed high RANTES levels (145±36pg/mL), while OA SF was characterised by only trace amount of this chemokine (2±1pg/mL). We found positive correlation of RANTES with chemotactic activity for mononuclear cells (LCA+MoCA;R=0.61;P<.05). Surprisingly, RANTES correlated also positively with neutrophiles number (R=0.77;P<0.001). Rheumatoid SF possesses strong chemotactic potency for leukocytes. RANTES is overexpressed in RA SF and is a potential mediator influencing intensity and composition of cellular infiltration in joints affected with inflammatory arthritis.

scholarly journals The Novel Role of MIF in the Secretion of IL-25, IL-31, and IL-33 from PBMC of Patients with Rheumatoid Arthritis

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4968
Author(s):  
Samuel García-Arellano ◽  
Luis Alexis Hernández-Palma ◽  
Sergio Cerpa-Cruz ◽  
Gabriela Athziri Sánchez-Zuno ◽  
Melva Guadalupe Herrera-Godina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Joint Destruction ◽  
Study Groups ◽  
Joint Disease ◽  
The Novel ◽  
Peripheral Blood Mononuclear ◽  
Cytokine Dysregulation ◽  
New Evidence

Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.

scholarly journals Il6/Sil6R Regulates Tnfα-Inflammatory Response In Synovial Fibroblasts Through Modulation of Transcriptional and Post-Transcriptional Mechanisms

2020 ◽  
Author(s):  
Alvaro Valin ◽  
Manuel J. Del Rey ◽  
Cristina Municio ◽  
Alicia Usategui ◽  
Marina Romero ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
De Novo ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Matrix Metalloproteases ◽  
P Value ◽  
Polymorphonuclear Cells ◽  
Expression Of Genes

Abstract Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods SF lines were stimulated with either TNFα or IL6 and sIL6R for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cicloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assesed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value < 0.05 was considered statistically significant. Results IL6/sIL6R stimulation of TNFα treated SF cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.

scholarly journals The role of meat in the expression of rheumatoid arthritis

2000 ◽  
Vol 84 (5) ◽  
pp. 589-595 ◽  
Author(s):  
William B. Grant
Keyword(s):  
Rheumatoid Arthritis ◽  
Short Review ◽  
Ecological Approach ◽  
Statistical Association ◽  
Prevalence Data ◽  
Statistical Correlations ◽  
Period 2 ◽  
Dietary Components ◽  
Synovial Tissues

Rheumatoid arthritis (RA) is characterized by inflammation of the synovial tissues in the joints. A number of papers related to dietary components that are associated with this inflammation are reviewed. In addition, the ecological approach is used to study the links between diet and RA. Multi-country data for prevalence of RA for females from eight and fifteen countries were compared statistically with components of national dietary supply. Fat from meat and offal for the period 2 years before the prevalence data was found to have the highest statistical association with the prevalence of RA (r2 0·877, P<0·001 for eight countries). The statistical correlations for meat and offal were almost as high as those for their fat. Similar correlations were found for temporal changes in indices of effects of RA in several European countries between 1968 and 1978 as more meat was added to the national diets, although the correlations were higher for meat than for fat. It is hypothesized that meat and offal may be a major factor contributing to the inflammation in RA. In the present short review, the author examines some of the data that associate meat consumption with RA and the possible factors, e.g. fat, Fe and nitrite, which may contribute to the inflammation.

scholarly journals TO008COMPARATIVE TRANSCRIPTOME AND CO-EXPRESSION NETWORK ANALYSIS REVEALED A POTENTIAL ROLE OF C1QB AND INTERFERON TYPE 1 PATHWAY IN CIRCULATING IMMUNE CELLS OF KIDNEY TRANSPLANTS PATIENTS WITH CHRONIC ANTIBODY MEDIATED REJECTION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gloria Santoro ◽  
Simona Granata ◽  
Paola Pontrelli ◽  
Mattia Rossi ◽  
Giovanni Gambaro ◽  
...  
Keyword(s):  
Network Analysis ◽  
Mononuclear Cells ◽  
Pathological Condition ◽  
Inflammatory Cells ◽  
Study Groups ◽  
Molecular Diagnostic ◽  
Peripheral Blood Mononuclear ◽  
Antibody Mediated Rejection

Abstract Background and Aims Chronic antibody-mediated rejection (CAMR) is a multifactorial pathological condition that can affect more that 40-50% of kidney allografts. Its clinical evolution is often silent, and this can delay its diagnosis. Although many advances in understanding the biological mechanisms underlying its onset/development, at the moment, no reliable non-invasive diagnostic biomarkers are available in clinic. Method We enrolled 29 patients with biopsy-proven CAMR, 29 stable transplant recipients (controls). Subsequently, the microarray profile of mRNA isolated from peripheral blood mononuclear cells (PBMCs) from 10 randomly selected CAMR patients and 10 controls was evaluated by Agilent technology. For the bioinformatics analysis we employed several statistical algorithms (including ANOVA and Kruskal-Wallis tests adjusted for multiple-tests) and a Weighted Gene Correlation Network Analysis (WGCNA) to select genes biologically associated in co-expressed networks. Results 935 genes resulted differentially expressed between the two study groups, demonstrating the large biological impact of this pathological condition on circulating immune-inflammatory cells. After WGCNA co-expression analysis, a group of genes (enclosed in a single co-expression module, 13 genes) resulted highly discriminating CAMR versus controls (p&lt;.5.2 e-7, FDR&lt;1%). This module included: Interferon-induced transmembrane proteins (IFITM) 2, 3, 4, confirming previous results by our group. However, the top discriminative gene was C1QB (Complement component 1, q subcomponent, B chain, p &lt;000.1), a key element involved in the classical complement pathway. ELISA confirmed the microarray results on the entire patients’ cohort. Conclusion Our study confirmed the role of the type 1 interferon pathway in CAMR and underlined its capability to promote C1QB expression. These effects could contribute to better define the role of innate immunity in CAMR. Finally, C1QB, if validated in a large cohort of patients, could represent a new valuable molecular diagnostic biomarker for this complication.

scholarly journals AB0109 THE ROLE OF CD70 IN THE DEVELOPMENT OF RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1353.1-1355
Author(s):  
S. J. Yoo ◽  
S. W. Kang ◽  
J. Kim ◽  
I. S. Yoo ◽  
C. K. Park ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Migration ◽  
Hypoxia Inducible Factor ◽  
Inflammatory Cells ◽  
Migration Assay ◽  
Allergy Immunol ◽  
Tnf Superfamily ◽  
Tnf Α ◽  
Inflammatory Molecules

Background:Rheumatoid arthritis (RA) is a progressive, chronic inflammatory autoimmune disease. Pro-inflammatory molecules, activated lymphocytes, and the migration of inflammatory cells are important in the development of RA. There are many unknown causes of RA. And there are many patients who are refractory to treatment with known disease-modifying anti-rheumatic drugs. So, unknown cause of RA needs to be elucidated.CD70 is a member of the tumor necrosis factor (TNF) superfamily and a ligand for CD27. The interaction of CD70 with its receptor CD27 promotes expansion and differentiation of memory and effector T cells as well as B-cell expansion and plasma cell differentiation. Hypoxia is an important micro-environmental factor in RA synovium. Hypoxia induces activation of hypoxia inducible factor (HIF). The expression of HIF-2α is up-regulated in human RA synovium. Reactive oxygen species (ROS) has been implicated in the pathophysiology of RA.Objectives:In this study, we tried to examine the presence of CD70 in RA synovium and investigate the role of CD70 in the development of RA associated with HIF-2α and ROS.Methods:Fibroblast-like synoviocyte (FLS), peripheral blood (PB) and synovial fluid (SF) were used for experiments. FLS was stimulated with recombinant human (rh)-IL-17 and rh-TNF-α. N-acetyl-L-cysteine (NAC) was used as a ROS scavenger. HIF-2α inhibitor (PT-2385) was used for examine the effect of HIF-2α in RA-FLS. RT-PCR, qPCR, western blotting, flow-cytometry, ELISA, cell migration assay, and scratch wound assay were performed.Results:CD70 mRNA is present and elevated by stimulation with IL-17 and TNF-α in both RA-FLS and osteoarthritis (OA)-FLS (Fig 1). CD70 also expresses on the surface of RA-FLS and OA FLS (Fig 2). CD70 expression on the surface of FLS is elevated by stimulation with IL-17 and TNF-α in both RA and OA. Soluble CD27 is present higher in the supernatant of RA-SF than OA-SF (Fig 3). HIF-2α mRNA, HIF-2α protein, and the amount of ROS were all elevated after treatment with IL-17 and TNF-α in RA-FLS (Fig 4, Fig 5). CD70 expression and the amount of ROS were lowered by treatment with HIF-2α inhibitor in RA-FLS (Fig 6). Decreased amount of ROS results in decreased CD70 expression on the RA-FLS (Fig 7). CD70 influenced on cell migration directly or by HIF-2α (Fig 8).Conclusion:In this study, we found the function of CD70 in RA-FLS associated with HIF-2α and ROS. First, CD70 on RA-FLS interacts with CD27 in the RA-SF and this interaction produces sCD27 (Fig. 9) and CD70 has an influence on the migration of RA-FLS. Second, IL-17 and TNF-α are critical factors to trigger the expression of CD70, HIF-2α and ROS in RA synovium. Third, CD70 is regulated by HIF-2α associated with ROS. From these results, we suggest that CD70 may be a new therapeutic target of RA. And sCD27 also may be an important diagnostic maker of RA.References:[1]Lundy SK, Sarkar S, Tesmer LA, Fox DA. Cells of the synovium in rheumatoid arthritis. T lymphocytes. Arthritis Res Ther. 2007;9(1):202.[2]Nevius E, Gomes AC, Pereira JP. Inflammatory Cell Migration in Rheumatoid Arthritis: A Comprehensive Review. Clin Rev Allergy Immunol. 2016;51(1):59-78.[3]Bowman MR, Crimmins MA, Yetz-Aldape J, Kriz R, Kelleher K, Herrmann S. The cloning of CD70 and its identification as the ligand for CD27. J Immunol. 1994;152(4):1756-61.[4]Kitajima S, Lee KL, Fujioka M, Sun W, You J, Chia GS, et al. Hypoxia-inducible factor-2 alpha up-regulates CD70 under hypoxia and enhances anchorage-independent growth and aggressiveness in cancer cells. Oncotarget. 2018;9(27):19123-35.[5]Gaber T, Dziurla R, Tripmacher R, Burmester GR, Buttgereit F. Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do! Ann Rheum Dis. 2005;64(7):971-80.Disclosure of Interests:None declared

Sex steroid receptors in rheumatoid arthritis

2004 ◽  
Vol 106 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Masato ISHIZUKA ◽  
Masahito HATORI ◽  
Takashi SUZUKI ◽  
Yasuhiro MIKI ◽  
Andrew D. DARNEL ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Relative Abundance ◽  
Sex Steroids ◽  
Steroid Receptors ◽  
Inflammatory Cells ◽  
Sex Steroid ◽  
Rt Pcr ◽  
Sex Steroid Receptors ◽  
Synovial Tissues

Rheumatoid arthritis (RA) is a disease characterized primarily by chronic inflammatory synovitis and is well-known to be associated with significant sex differences in its prevalence and clinical features. Sex steroids have been proposed to be involved in the pathogenesis of RA, but details pertaining to the expression of sex steroid receptors in RA synovial tissue have yet to be fully characterized. In the present study, we examined oestrogen receptor (ER) α, ERβ, progesterone receptor (PR) and androgen receptor (AR) mRNA expression using real-time reverse transcriptase–PCR (RT-PCR) in eight female RA synovial tissues and six female synovial tissues without inflammation, and determined immunolocalization of ERα, ERβ, PR-A, PR-B and AR using immunohistochemistry in synovial tissues obtained from 22 RA patients. Real-time RT-PCR analysis demonstrated the expression of ER, PR and AR mRNAs in both RA and non-inflamed synovial tissues. Relative abundance of ER mRNAs was significantly higher in RA synovial tissue than non-inflamed synovial tissue (P<0.05). In addition, the relative ERα/ERβ mRNA expression ratio was significantly lower in RA than non-inflamed synovial tissue (RA, 2.34±1.60; and non-inflamed, 20.7±19.1; P<0.05). There were no significant differences in relative abundance of PR mRNA. Relative abundance of AR mRNA was significantly lower in RA (P<0.05). Immunoreactivity for ERα, ERβ, PR-B and AR was detected in the lining cells, inflammatory cells and fibroblasts in all the patients examined. The labelling indices for ERβ and PR-B were more abundant in both lining cells (ERβ, 54.2±12.2%; PR-B, 73.6±18.9%) and inflammatory cells (ERβ, 74.6±16.2%; PR-B, 75.9±16.1%) than in fibroblasts (ERβ, 36.5±15.6%; PR-B, 49.4±18.0%). Labelling indices for ERα and AR were significantly higher in lining cells (ERα, 14.4±8.6%; AR, 31.2±11.3%) and fibroblasts (ERα, 12.1±7.5%; AR, 20.1±9.6%) than those in inflammatory cells (ERα, 5.7±3.3%; AR, 9.2±4.4%). There were significant differences (P<0.05) in the labelling indices for ERα, ERβ and PR-B between men and women under 50 years of age in fibroblasts of RA synovial tissues. These results indicate that sex steroid receptors are present in RA and non-inflamed synovial tissues, including inflammatory cells in RA, and suggest that sex steroids may play important roles in the regulation of inflammation of RA synovial tissue.

Platelets Protect Tumors from Hemorrhage Induced by Stroma-Infiltrating Leukocytes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3916-3916
Author(s):  
Benoit H Ho-Tin-Noe ◽  
Carla Carbo ◽  
Melanie Demers ◽  
Stephen M Cifuni ◽  
Tobias Goerge ◽  
...  
Keyword(s):  
Tumor Stroma ◽  
Inflammatory Cells ◽  
Skin Inflammation ◽  
Genetically Engineered ◽  
Leukocyte Transmigration ◽  
Genetically Engineered Mice ◽  
Tumor Bleeding ◽  
Massive Accumulation

Abstract In a recent study, we showed that platelets are crucial regulators of tumor vascular homeostasis in that they continuously prevent tumor hemorrhage through secretion of their granules. However, it remains unclear what platelets target to prevent tumor bleeding. Tumors are associated with inflammation, a cause of hemorrhage in thrombocytopenia. We hypothesized that platelets protect tumors from vascular damages induced by infiltrating inflammatory cells. Here, we report that thrombocytopenia-induced tumor hemorrhage preferentially occurs at the periphery of tumors, where massive accumulation of monocytes/macrophages and neutrophils was revealed by tumor histology. To further investigate the role of tumor-infiltrating leukocytes in the induction of tumor hemorrhage in thrombocytopenic mice, we used genetically-engineered mice with a deficiency in either beta2 or beta3 integrins, or in integrin activation. We show that these mice have decreased leukocyte infiltration in the tumor stroma and are protected from thrombocytopenia-induced tumor hemorrhage. Using a model of TNFa-induced skin inflammation, we demonstrate that releasates from collagen- and thrombin-stimulated platelets inhibit neutrophil-induced vascular damage. Our results show that platelets protect tumors from vascular leakage induced by infiltrating leukocytes and that releasate from activated platelets has potent in vivo healing properties needed after leukocyte transmigration.

Effects of the Neuropeptide, Substance P, on Lymphocyte Proliferation in Rheumatoid Arthritis

1995 ◽  
Vol 23 (6) ◽  
pp. 431-438 ◽  
Author(s):  
M Jovas ◽  
L A Pinto ◽  
J A Pereira da Silva ◽  
R M M Victorino
Keyword(s):  
Rheumatoid Arthritis ◽  
Substance P ◽  
Lymphocyte Proliferation ◽  
Mononuclear Cells ◽  
Thymidine Incorporation ◽  
Lymphocyte Activation ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Dose Dependent

There is evidence supporting the involvement of the neuropeptide, substance P, in the pathogenesis of rheumatoid arthritis. In view of the suggested role of T-cells in this disease, we have investigated the effects of substance P on mitogen-induced lymphocyte proliferation in rheumatoid arthritis patients. The peripheral blood mononuclear cells from 20 patients with rheumatoid arthritis and 25 controls were cultured in the presence or absence of substance P (10−-10 M to 10−-6 M) and stimulated with phytohaemagglutinin or concanavalin A. After 3 days of culture the proliferative responses were determined by measuring [3H]thymidine incorporation into the cells. Substance P enhanced, in a dose-dependent manner, the lymphocyte proliferative responses both in rheumatoid arthritis patients and in controls. Although there was a trend towards a greater enhancing effect in the rheumatoid arthritis patients, this was not statistically significant. Some individual patients with rheumatoid arthritis showed enhancements of lymphocyte proliferation with substance P that were clearly outside the range seen in healthy controls. The possibility that substance P has a role in the pathogenesis of rheumatoid arthritis through the up-regulation of lymphocyte activation should be considered in further studies of the immunomodulatory properties of substance P in arthritis.

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