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Mycophenolic Acid Influences T Helper 2 (Th2) Cytokine Induced Expression of Intercellular Cell Adhesion Molecule -1 (ICAM-1) on Human Endothelial Cells

  • Guenter Weigel , Peter Bertalanffy , Peter Dubsky , Andrea Griesmacher and Ernst Wolner
Published/Copyright: June 1, 2005
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Volume 37 Issue 3

Abstract

A possible synergistic effect of mycophenolic acid (MPA) and the immunosuppressive cytokines IL-4, IL-10 and IL-13 was investigated in human umbilical vein endothelial cells (HUVEC). These cytokines, which are produced by Th2-lymphocytes, were shown to induce the expression of vascular cell adhesion molecule-1 (VCAM-1) and production of IL-6 in endothelial cells. In this study we found IL-4 to induce both intercellular cell adhesion molecule-1 (ICAM-1) and VCAM-1 expression, whereas IL-13 induced VCAM-1 only. The surface expression of E-selectin was not influenced by any of the cytokines tested. MPA on its own led to statistically significant ICAM-1 expression on HUVEC. The combination of MPA with IL-4 led to a significant ICAM-1 expression in an additive manner compared to the cytokine alone. In contrast, MPA neither induced VCAM-1 nor did it influence the effects of IL-4 and IL-13 on VCAM-1 expression. A clinically relevant concentration of mycophenolic acid (10 μmol/l) decreased intracellular guanosine-5′-triphosphate (GTP) levels significantly. Since intracellular nucleotides are responsible for the glycosylation of proteins, a disturbance of the endothelial nucleotide balance could be responsible for the effects of MPA on ICAM-1. Guanine and guanosine prevented and partially reversed the actions of MPA, on both intracellular GTP and ICAM-1 expression, which strongly implies that MPA by interfering with nucleotide metabolism, affects the adhesive properties of endothelial cells, and by acting synergistically with IL-4 probably influences Th2 cytokine effects.

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Published Online: 2005-06-01
Published in Print: 1999-03-01

Copyright (c)1999 by Walter de Gruyter GmbH & Co. KG

Articles in the same Issue

  1. IFCC/Beckman European Conference 1998 Frontiers in Molecular Basis of Disease: Inflammatory Diseases
  2. Frontiers in Molecular Basis of Disease: Inflammatory Diseases
  3. Mechanisms of Antigen Presentation
  4. How to Extinguish Lymphocyte Activation, Immunotyrosine-Based Inhibition Motif (ITIM)-Bearing Molecules a Solution?
  5. Association between Reduced Human Leukocyte Antigen (HLA)-DR Expression on Blood Monocytes and Increased Plasma Level of Interleukin-10 in Patients with Severe Burns
  6. Immunostimulatory CpG Motifs Trigger a T Helper-1 Immune Response to Human Immunodeficiency Virus Type-1 (HIV-1) gp160 Envelope Proteins
  7. Activation and Regulation of NFκB during Acute Inflammation
  8. CD 14++ Monocytes, CD14+/CD16+ Subset and Soluble CD14 as Biological Markers of Inflammatory Systemic Diseases and Monitoring Immuno-suppressive Therapy
  9. A Potential Role of an Intracellular Signaling Defect in Neutrophil Functional Abnormalities and Promotion of Tissue Damage in Patients with Localized Juvenile Periodontitis
  10. Polymorphonuclear Oxidative Burst after Helicobacter pylori Water Extract Stimulation Is not Influenced by the Cytotoxic Genotype but Indicates Infection and Gastritis Grade
  11. Flow Cytometry of Cerebrospinal Fluid (CSF) Lymphocytes: Alterations of Blood/CSF Ratios of Lymphocyte Subsets in Inflammation Disorders of Human Central Nervous System (CNS)
  12. Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions
  13. Mycophenolic Acid Influences T Helper 2 (Th2) Cytokine Induced Expression of Intercellular Cell Adhesion Molecule -1 (ICAM-1) on Human Endothelial Cells
  14. Alterations of Endothelial Nucleotide Levels by Mycophenolic Acid Result in Changes of Membrane Glycosylation and E-Selectin Expression
  15. C-Reactive Protein: Structural Biology and Host Defense Function
  16. A Novel Acute-Phase Marker: Lipopolysaccharide Binding Protein (LBP)
  17. Detection of Acute Phase Response and Infection. The Role of Procalcitonin and C-Reactive Protein
  18. Lactoferrin: A Multifunctional Glycoprotein Involved in the Modulation of the Inflammatory Process
  19. Annexin V and Phospholipid Metabolism
  20. Regulation of Leukocyte Trafficking by Lipoxins
  21. Lipoxin and Aspirin-Triggered 15-epi-Lipoxin Cellular Interactions Anti-Inflammatory Lipid Mediators
  22. Differentiation and Assessment of Cell Death
  23. Depending on Their Concentration Oxidized Low Density Lipoproteins Stimulate Extracellular Matrix Synthesis or Induce Apoptosis in Human Coronary Artery Smooth Muscle Cells
  24. Apheresis of Plasma Compounds as a Therapeutic Principle in Severe Sepsis and Multiorgan Dysfunction Syndrome
  25. Supportive Therapy of the Sepsis Syndrome
  26. Supplemental Immune Globulins in Sepsis
  27. Polymorphonuclear Granulocyte Stimulation by Cellulose-Based Hemodialysis Membranes
  28. Reduction of Circulating Cholesterol and Apolipoprotein Levels during Sepsis
  29. Outcome Prediction by Traditional and New Markers of Inflammation in Patients with Sepsis
  30. Isolation of Highly Enriched Human Monocytes from Ten ml Samples of Heparinised Whole Blood
  31. Endotoxin Adsorbant Based on Immobilized Human Serum Albumin
https://doi.org/10.1515/CCLM.1999.044

Articles in the same Issue

  1. IFCC/Beckman European Conference 1998 Frontiers in Molecular Basis of Disease: Inflammatory Diseases
  2. Frontiers in Molecular Basis of Disease: Inflammatory Diseases
  3. Mechanisms of Antigen Presentation
  4. How to Extinguish Lymphocyte Activation, Immunotyrosine-Based Inhibition Motif (ITIM)-Bearing Molecules a Solution?
  5. Association between Reduced Human Leukocyte Antigen (HLA)-DR Expression on Blood Monocytes and Increased Plasma Level of Interleukin-10 in Patients with Severe Burns
  6. Immunostimulatory CpG Motifs Trigger a T Helper-1 Immune Response to Human Immunodeficiency Virus Type-1 (HIV-1) gp160 Envelope Proteins
  7. Activation and Regulation of NFκB during Acute Inflammation
  8. CD 14++ Monocytes, CD14+/CD16+ Subset and Soluble CD14 as Biological Markers of Inflammatory Systemic Diseases and Monitoring Immuno-suppressive Therapy
  9. A Potential Role of an Intracellular Signaling Defect in Neutrophil Functional Abnormalities and Promotion of Tissue Damage in Patients with Localized Juvenile Periodontitis
  10. Polymorphonuclear Oxidative Burst after Helicobacter pylori Water Extract Stimulation Is not Influenced by the Cytotoxic Genotype but Indicates Infection and Gastritis Grade
  11. Flow Cytometry of Cerebrospinal Fluid (CSF) Lymphocytes: Alterations of Blood/CSF Ratios of Lymphocyte Subsets in Inflammation Disorders of Human Central Nervous System (CNS)
  12. Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions
  13. Mycophenolic Acid Influences T Helper 2 (Th2) Cytokine Induced Expression of Intercellular Cell Adhesion Molecule -1 (ICAM-1) on Human Endothelial Cells
  14. Alterations of Endothelial Nucleotide Levels by Mycophenolic Acid Result in Changes of Membrane Glycosylation and E-Selectin Expression
  15. C-Reactive Protein: Structural Biology and Host Defense Function
  16. A Novel Acute-Phase Marker: Lipopolysaccharide Binding Protein (LBP)
  17. Detection of Acute Phase Response and Infection. The Role of Procalcitonin and C-Reactive Protein
  18. Lactoferrin: A Multifunctional Glycoprotein Involved in the Modulation of the Inflammatory Process
  19. Annexin V and Phospholipid Metabolism
  20. Regulation of Leukocyte Trafficking by Lipoxins
  21. Lipoxin and Aspirin-Triggered 15-epi-Lipoxin Cellular Interactions Anti-Inflammatory Lipid Mediators
  22. Differentiation and Assessment of Cell Death
  23. Depending on Their Concentration Oxidized Low Density Lipoproteins Stimulate Extracellular Matrix Synthesis or Induce Apoptosis in Human Coronary Artery Smooth Muscle Cells
  24. Apheresis of Plasma Compounds as a Therapeutic Principle in Severe Sepsis and Multiorgan Dysfunction Syndrome
  25. Supportive Therapy of the Sepsis Syndrome
  26. Supplemental Immune Globulins in Sepsis
  27. Polymorphonuclear Granulocyte Stimulation by Cellulose-Based Hemodialysis Membranes
  28. Reduction of Circulating Cholesterol and Apolipoprotein Levels during Sepsis
  29. Outcome Prediction by Traditional and New Markers of Inflammation in Patients with Sepsis
  30. Isolation of Highly Enriched Human Monocytes from Ten ml Samples of Heparinised Whole Blood
  31. Endotoxin Adsorbant Based on Immobilized Human Serum Albumin
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