Sphingoid bases induce dose-dependent cytotoxicity and cytokine responses in human myeloid dendritic cells

Abstract

Conclusion: Sphingoid bases exhibit dose-dependent cytotoxicity and cytokine responses against human myeloid dendritic cells. But at physiologic concentrations sphingoid bases appear to be safe and efficacious at the doses needed to prevent or treat microbial infections in the oral cavity. v TABLE OF CONTENTS LIST OF TABLES vii LIST OF FIGURES viii CHAPTER 1. INTRODUCTION 1.1. Periodontitis 1.2. The prevalence of periodontitis 1.3. Risk factors periodontitis 1.4. Pathogens of periodontitis 1.5. Salivary components 1.6. Sphingoid bases 1.6.1. Sphingoid base structure 1.6.2. Sphingoid base function 1.6.3. Role in inflammation CHAPTER 2. HYPOTHESIS AND SPECIFIC AIMS CHAPTER 3. MATERIAL AND METHODS 3.1. Media, solutions and inocula 3.2. Preparation of HagB 3.3. Preparation of sphingoid bases 3.4. Preparation of human myeloid dendritic cells 3.5. Cytotoxicity 3.6. Luminex 3.7. Establish HagB as a potent pro-inflammatory stimulus 3.8. Establish working doses of sphingoid bases 3.9. Effect of sphingoid bases on dendritic cells 3.10. Statistical Analysis CHAPTER 4. RESULTS 4.1. The ability of HagB to induce chemokine and cytokine responses in human myeloid dendritic cells 4.2. Establish P. gingivalis HagB as a potent pro-inflammatory stimulus 4.3. The effect of sphingoid bases on the HagB-induced chemokine and cytokine responses 4.4. The cytotoxicity of sphingoid bases on human myeloid dendritic cells 4.5. The ability of sphingoid bases to attenuate HagB-induced chemokine and cytokine responses CHAPTER 5. DISCUSSION vi