dc.contributor.author |
Moodad, Sara Hisham, |
dc.date.accessioned |
2017-08-30T14:12:36Z |
dc.date.available |
2017-08-30T14:12:36Z |
dc.date.issued |
2015 |
dc.date.submitted |
2015 |
dc.identifier.other |
b18360816 |
dc.identifier.uri |
http://hdl.handle.net/10938/10832 |
dc.description |
Thesis. M.Sc. American University of Beirut. Department of Experimental Pathology, Microbiology, and Immunology of the Faculty of Medicine 2015. W 4 M817e 2015 |
dc.description |
Advisor: Alexander Abdelnoor, PHD, Professor, Department of Experimental Pathology, Immunology and Microbiology ; Committee members: Dr. Joseph Simaan, MD, Professor, Department of Pharmacology and Toxicology ; Dr. Ghassan Matar, PHD, Professor, Department of Experimental Pathology, Immunology and Microbiology ; Dr. Elias Rahal, PHD, Assistant professor, Department of Experimental Pathology, Immunology and Microbiology. |
dc.description |
Includes bibliographical references (leaves 44-50) |
dc.description.abstract |
Background and aims: The role of Toll-Like Receptor-4 (TLR-4) in innate immunity and inflammation is well established. Lipopolysaccharide (LPS) a constituent of the cell wall of Gram negative bacteria is a ligand for TLR-4. Binding of LPS to TLR-4 activates both myeloid differentiation (MyD88) dependent and independent pathways leading to the production of excessive amount of pro-inflammatory cytokines, including Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-12 (IL-12). The excess production of cytokines can lead to hypotension and shock, in some patients with Gram negative infections. Previous studies have shown that endogenous adenosine, an anti-inflammatory agent, is released at sites of injury and inflammation thereby decreasing the excessive production of cytokines. On the other hand, caffeine, a non-specific adenosine blocker, has been reported in several studies to have opposing immune-modulatory effects. In this study, the effects of caffeine and adenosine on TLR-4 in promoting or decreasing the production of TNF-α and IL-12 by LPS-stimulated monocytes was investigated.Methods: Monocytes were isolated using Pluribead® kit from pooled blood obtained from ten volunteers. The monocytes were then incubated for 24 hours with LPS extracted from Escherichia coli (aTLR-4 ligand activator) , adenosine, caffeine and LPS extracted from Rhodobacter sphaeroides (LPS-RS, a TLR-4 ligand blocker), each alone or in different combinations. Later, the levels of pro-inflammatory cytokines TNFα and IL-12 were assessed using an Enzyme Linked ImmunoAssay (ELISA). Results: Caffeine and adenosine significantly reduced the amount of TNFα and IL-12 produced by LPS-stimulated monocytes. Regarding non-stimulated and LPS-RS blocked monocytes, the presence of adenosine and caffeine significantly decreased TNFα levels produced by these cells but had little or non-significant effect on the levels of IL-12.Conclusion: Both caffeine and adenosine block the production of the pro-inflammatory cytok |
dc.format.extent |
1 online resource ( 64 leaves ) |
dc.language.iso |
eng |
dc.relation.ispartof |
Theses, Dissertations, and Projects |
dc.subject.classification |
W 4 M817e 2015 |
dc.subject.lcsh |
Dissertations, Academic. |
dc.subject.lcsh |
Adenosine. |
dc.subject.lcsh |
Caffeine. |
dc.title |
Effect of adenosine and caffeine on Toll-Like Receptor-4 (TLR-4) - |
dc.type |
Thesis |
dc.contributor.department |
Department of Experimental Pathology, Microbiology, and Immunology, Faculty of Medicine, |
dc.contributor.institution |
American University of Beirut. |