Influence of β-D-mannuronic acid, as a new member of non-steroidal anti-inflammatory drugs family, on expression pattern of chemokines and their receptors in rheumatoid arthritis

Background: : Based on the encouraging results of phase III clinical trial of β-D-mannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. Methods:: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 μg/mL) of M2000 and optimum dose (1 μg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. Results:: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression down-regulated significantly followed by treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by treatment of these cells with high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by treatment of these cells with high dose of M2000 and optimum dose of diclofenac. Conclusion:: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.

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Differential expression of CD11b/CD18 (Mo1) and myeloperoxidase genes during myeloid differentiation

Blood ◽

10.1182/blood.v73.1.131.bloodjournal731131 ◽

1989 ◽

Vol 73 (1) ◽

pp. 131-136 ◽

Cited By ~ 2

Author(s):

AG Rosmarin ◽

SC Weil ◽

GL Rosner ◽

JD Griffin ◽

MA Arnaout ◽

...

Keyword(s):

Cell Surface ◽

Mrna Expression ◽

Cell Adhesion Molecule ◽

Surface Expression ◽

Cell Surface Expression ◽

Myeloid Differentiation ◽

Mrna Levels ◽

Acute Nonlymphocytic Leukemia ◽

Specific Proteins ◽

Early Human

During the course of differentiation of early human myeloid cells toward monocytes and granulocytes, cell surface expression of the cell adhesion molecule, CD11b/CD18 (Mo1) increases dramatically and expression of myeloperoxidase (MPO), a bacteriocidal enzyme, decreases markedly. Using the inducible promyelocytic cell line HL-60 as a model, we studied the mRNA expression of these genes. Differentiation of these cells along both a monocytic and a granulocytic pathway demonstrated that the mRNA levels of the two subunits of CD11b/CD18 increased in a pattern temporally and quantitatively similar to the increase in cell surface expression of this heterodimer. In contrast, the expression of MPO mRNA decreased in a temporal and quantitative pattern similar to the known decrease in MPO protein during differentiation, suggesting that regulation of these myeloid-specific proteins may occur at the level of mRNA expression. These findings have important implications with regard to the nature of the block in differentiation in acute nonlymphocytic leukemia and the regulation of myeloid gene expression.

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Cell Surface Expression of ICAM-1 (CD54) and LFA-3 (CD58), Two Adhesion Molecules, Is Up-Regulated on Bone Marrow Leukemic Blasts After In Vivo Administration of High-Dose Recombinant Interleukin-2

Journal of Immunotherapy ◽

10.1097/00002371-199112000-00004 ◽

1991 ◽

Vol 10 (6) ◽

pp. 412-417 ◽

Cited By ~ 11

Author(s):

Daniel Olive ◽

Marc Lopez ◽

Didier Blaise ◽

Patrice Viens ◽

Anne-Marie Stoppa ◽

...

Keyword(s):

Bone Marrow ◽

Cell Surface ◽

Adhesion Molecules ◽

Interleukin 2 ◽

Surface Expression ◽

Cell Surface Expression ◽

High Dose ◽

Recombinant Interleukin 2 ◽

In Vivo Administration

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Differential expression of CD11b/CD18 (Mo1) and myeloperoxidase genes during myeloid differentiation

Blood ◽

10.1182/blood.v73.1.131.131 ◽

1989 ◽

Vol 73 (1) ◽

pp. 131-136 ◽

Cited By ~ 79

Author(s):

AG Rosmarin ◽

SC Weil ◽

GL Rosner ◽

JD Griffin ◽

MA Arnaout ◽

...

Keyword(s):

Cell Surface ◽

Mrna Expression ◽

Cell Adhesion Molecule ◽

Surface Expression ◽

Cell Surface Expression ◽

Myeloid Differentiation ◽

Mrna Levels ◽

Acute Nonlymphocytic Leukemia ◽

Specific Proteins ◽

Early Human

Abstract During the course of differentiation of early human myeloid cells toward monocytes and granulocytes, cell surface expression of the cell adhesion molecule, CD11b/CD18 (Mo1) increases dramatically and expression of myeloperoxidase (MPO), a bacteriocidal enzyme, decreases markedly. Using the inducible promyelocytic cell line HL-60 as a model, we studied the mRNA expression of these genes. Differentiation of these cells along both a monocytic and a granulocytic pathway demonstrated that the mRNA levels of the two subunits of CD11b/CD18 increased in a pattern temporally and quantitatively similar to the increase in cell surface expression of this heterodimer. In contrast, the expression of MPO mRNA decreased in a temporal and quantitative pattern similar to the known decrease in MPO protein during differentiation, suggesting that regulation of these myeloid-specific proteins may occur at the level of mRNA expression. These findings have important implications with regard to the nature of the block in differentiation in acute nonlymphocytic leukemia and the regulation of myeloid gene expression.

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TNF-αAutocrine Feedback Loops in Human Monocytes: The Pro- and Anti-Inflammatory Roles of the TNF-αReceptors Support the Concept of Selective TNFR1 BlockadeIn Vivo

Journal of Immunology Research ◽

10.1155/2016/1079851 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 19

Author(s):

Jennie M. Gane ◽

Robert A. Stockley ◽

Elizabeth Sapey

Keyword(s):

Cell Surface ◽

Inflammatory Cytokine ◽

Human Subjects ◽

Expression Patterns ◽

Surface Expression ◽

Cell Surface Expression ◽

Human Monocytes ◽

Healthy Human ◽

Anti Inflammatory

Selective TNFR1 blockade in inflammatory diseases is emerging as a clinical strategy. We studied the roles of the two TNF-αreceptors, TNFR1 and TNFR2, in human monocytes, the principal producer of TNF-αand central to many TNF-αdriven diseases. We hypothesised that TNF-αhas pro- and anti-inflammatory effects on monocytes, occurring differentially via TNFR1 and TNFR2. Monocytes were isolated from healthy human subjects and exposed to LPS, plus/minus the addition of blocking antibodies to TNF-αor its receptors. Pro- and anti-inflammatory cytokine production was quantified using real-time PCR and ELISAs. Cell surface expression of TNFR1/2 was measured by flow cytometry. We demonstrated that monocytes vary in the expression patterns of TNFR1 and TNFR2. Autocrine binding of TNF-αled to sustained upregulation of proinflammatory cytokines via TNFR1. In contrast, autocrine binding via TNFR2 upregulated theanti-inflammatory cytokine, IL-10, without proinflammatory effect. TNFR2 was responsible for binding soluble TNF-αsecreted by monocytes, clearing the cytokine from the pericellular environment. TNFR1 blockade did not change the cell surface expression of TNFR2, leaving this receptor free to upregulate IL-10. These novel results support the concept of selective TNFR1 blockadein vivoin order that positive anti-inflammatory effects of TNF-αcan be retained via TNFR2 ligation.

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Differential effects of mitomycin C and doxorubicin on P-glycoprotein expression

Biochemical Journal ◽

10.1042/bj3550617 ◽

2001 ◽

Vol 355 (3) ◽

pp. 617-624 ◽

Cited By ~ 36

Author(s):

Rangan MAITRA ◽

Patricia A. HALPIN ◽

Katherine H. KARLSON ◽

Rodney L. PAGE ◽

Daniel Y. PAIK ◽

...

Keyword(s):

Gene Expression ◽

Cell Surface ◽

Mrna Expression ◽

Mitomycin C ◽

Surface Expression ◽

Mdr1 Gene ◽

Cell Surface Expression ◽

Differential Effects ◽

P Glycoprotein ◽

And Function

Previous studies have demonstrated that mitomycin C (MMC) and other DNA cross-linking agents can suppress MDR1 (multidrug resistance 1) gene expression and subsequent functional P-glycoprotein (Pgp) expression, whereas doxorubicin and other anthracyclines increase MDR1 gene expression. In the present study, with stably transfected Madin–Darby canine kidney C7 epithelial cells expressing a human Pgp tagged with green fluorescent protein under the proximal human MDR1 gene promoter, we demonstrated that MMC and doxorubicin have differential effects on Pgp expression and function. Doxorubicin caused a progressive increase in the cell-surface expression of Pgp and function. In contrast, MMC initially increased plasma membrane expression and function at a time when total cellular Pgp was constant and Pgp mRNA expression had been shown to be suppressed. This was followed by a rapid and sustained decrease in cell-surface expression at later times, presumably as a consequence of the initial decrease in mRNA expression. These studies imply that there are at least two independent chemosensitive steps that can alter Pgp biogenesis: one at the level of mRNA transcription and the other at the level of Pgp trafficking. Understanding the combined consequences of these two mechanisms might lead to novel chemotherapeutic approaches to overcoming drug resistance in human cancers by altering either Pgp mRNA expression or trafficking to the membrane.

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The Inhibitory Role of M2000 (β-D-Mannuronic Acid) on Expression of Toll-like Receptor 2 and 4 in HT29 Cell Line

Recent Patents on Inflammation & Allergy Drug Discovery ◽

10.2174/1872213x13666181211160238 ◽

2019 ◽

Vol 13 (1) ◽

pp. 57-65

Author(s):

Laleh Sharifi ◽

Mona Moshiri ◽

Mohammad M.S. Dallal ◽

Mohammad H. Asgardoon ◽

Maryam Nourizadeh ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Cell Line ◽

Inflammatory Responses ◽

Cell Model ◽

Hek293 Cells ◽

Mannuronic Acid ◽

Tlr4 Mrna ◽

Anti Inflammatory ◽

High Doses

Background/Objectives: Anti-inflammatory agents play a crucial role in controlling inflammatory diseases such as Inflammatory Bowel Disease (IBD) but their use is restricted due to their vast side effects. M2000 (β-D-mannuronic acid) is a new immunomodulatory drug. According to the capacity of M2000 in suppressing some molecules involved in Toll Like Receptors (TLRs) signaling and reducing oxidative stress we hypothesize that, this molecule may have a potential role in decreasing inflammatory responses in IBD. The aim of this study was to evaluate the cytotoxicity of M2000 and its effect on the gene expression of TLR2 and TLR4. Methods: HEK293 cell line was grown and divided into 96-well cell plate and MTT assay was performed. HT29 cells were cultured and treated with low and high doses of M2000. Total RNA was extracted and cDNA synthesized and quantitative real-time PCR was done to quantify the TLR2 and TLR4 mRNA expression. Results: We found that M2000 at the concentration of ≤ 1000µg/ml had no obvious cytotoxicity effect on the HEK293 cells. Also, low and high doses of M2000 could significantly down-regulate both TLR2 and TLR4 mRNA expression. Moreover, a significant reduction in gene expression of TLR2 and TLR4 in an inflammatory condition resulted in high doses of M2000 in the presence of LPS. Conclusion: Our study which was conducted in colonic epithelial cell model, shows that M2000 can be considered as a new anti-inflammatory agent in IBD. However, more comprehensive experimental and clinical studies are required to recognize the molecular mechanism of M2000 and also its safety and efficacy.

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CD150 AND CD180 ARE INVOLVED IN REGULATION OF TRANSCRIPTION FACTORS EXPRESSION IN CHRONIC LYMPHOCYTIC LEUKEMIA CELLS

Experimental Oncology ◽

10.31768/2312-8852.2017.39(4):291-298 ◽

2017 ◽

Vol 39 (4) ◽

pp. 291-298 ◽

Cited By ~ 1

Author(s):

I M Gordienko ◽

L M Shlapatska ◽

V M Kholodniuk ◽

L M Kovalevska ◽

T S Ivanivskaya ◽

...

Keyword(s):

B Cells ◽

Chronic Lymphocytic Leukemia ◽

Cell Surface ◽

B Cell ◽

Mrna Expression ◽

Mrna Level ◽

Surface Expression ◽

Lymphocytic Leukemia ◽

Cell Surface Expression ◽

B Lineage

Background: Sequential stages of B-cell development is stringently coordinated by transcription factors (TFs) network that include B-lineage commitment TFs (Ikaros, Runx1/Cbfb, E2A, and FOXO1), B-lineage maintenance TFs (EBF1 and PAX5) and stage specific set of TFs (IRF4, IRF8, BCL6, BLIMP1). Deregulation of TFs expression and activity is often occurs in malignant B cells. The aim of this study was to evaluate TFs expression in chronic lymphocytic leukemia cells taking into consideration CD150 cell surface expression. From other side we attempted to regulate TFs expression via CD150 and CD180 cell surface receptors. Materials and Methods: Studies were performed on normal peripheral blood B-cell subpopulations and chronic lymphocytic leukemia (CLL) cells isolated from peripheral blood of 67 primary untreated patients with CLL. Evaluation of TFs expression was performed on mRNA level using qRT-PCR and on protein level by western blot analysis. Results: Median of PAX5 and EBF1 mRNA expression was higher in cell surface CD150 positive (csCD150+) compared to csCD150- CLL cases or normal CD19+ and CD19+CD5+ B-cell subsets. Differences in mRNA expression of IRF8, IRF4 and BLIMP1 between studied groups of CLL and normal B cells were not revealed. All CLL cases were characterized by downregulated expression of PU.1 and BCL6 mRNAs in comparison to normal B cells. At the same time elevated SPIB mRNA expression level was restricted to CLL cells. Protein expression of IRF4, IRF8 and BCL6 was uniformly distributed between csCD150- and csCD150+ CLL cases. PU.1 protein and CD20 that is direct PU.1 target gene positively correlated with CD150 cell surface expression on CLL cells. Ligation of CD150 and CD180 alone or in combination upregulated IRF8 and PU.1 while downregulated the IRF4 mRNA expression. Signaling via CD150 or CD180 alone elevated the level of BCL6 mRNA. Strong downregulation of IRF4 mRNA was observed after CD150, CD180 or CD150 and CD180 coligation on CLL cells. We found that in CLL cells CD150 is a negative regulator of SPIB while CD180 is involved in upregulation of EBF1 expression level. Moreover, CD180 ligation on CLL cells caused increase of CD150 mRNA level that is a one of the EBF1 target genes. Conclusions: Analysis of TFs expression profile revealed upregulated SPIB mRNA level and downregulated PU.1 in CLL cells. CD150 and CD180 receptors may modulate transcriptional program in CLL cells by regulating the TFs expression levels.

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