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dc.contributor.authorZawawi, Khalid Hashimen_US
dc.date.accessioned2018-09-18T15:34:52Z
dc.date.available2018-09-18T15:34:52Z
dc.date.issued2004
dc.date.submitted2004
dc.identifier.other(OCoLC)57045500
dc.identifier.otherb25313046
dc.identifier.urihttps://hdl.handle.net/2144/31303
dc.descriptionThesis (D.Sc.)--Boston University, Henry M. Goldman School of Dental Medicine, 2004 (Oral Biology).en_US
dc.descriptionIncludes bibliography (leaves 107-151).en_US
dc.description.abstractLipopolysaccharide (LPS), a glycolipid found in the outer membrane of Gram negative bacteria, induces the secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-a) and interleukin (IL )-1, by monocytes/macrophages. Excessive and uncontrolled secretion of these compounds leads to multiple pathological conditions, such as septic shock. LPS receptors have been shown to be CD14, TLR4 and MD-2. LPS interaction with these receptors mediates many monocyte/macrophage functions. Even though only CD14 was demonstrated to bind to LPS, and TLR4/MD-2 were capable of transducing signals, data only show that LPS and CD 14 were in close proximity to TLR4 and no direct binding was reported. Quite recently, moesin, a member of the ERM family of proteins, has been also found to function as a receptor for LPS. We have shown that anti-moesin antibody inhibited the release of TNFa by LPS stimulated monocytes. Moesin was also found to be necessary for the detection of LPS, where homozygous knockout mice exhibited 3-fold reduction in neutrophil infiltrates in LPS injected sites when compared to their wild type controls. When moesin gene expression was completely suppressed with antisense oligonucleotides, there was a significant reduction of LPS-induced TNF-a secretion. LPS stimulation of mononuclear phagocytes activates several intracellular signaling pathways including the phosphorylation of IKBa, mitogen-activated protein kinase (MAPK) pathways: extracellular signal-regulated kinases (ERK) 1 / 2 (P44/42), p38. These signaling pathways in tum activate a variety of transcription factors including NF-KB, which coordinates the induction of several genes encoding inflammatory mediators. [TRUNCATED]en_US
dc.language.isoen_US
dc.publisherBoston Universityen_US
dc.rightsThis work is being made available in OpenBU by permission of its author, and is available for research purposes only. All rights are reserved to the author.en_US
dc.subjectGram-negative bacteriaen_US
dc.subjectLipopolysaccharidesen_US
dc.subjectMacrophagesen_US
dc.subjectMoesinen_US
dc.titleMoesin mediated intracellular signalling in LPS-stimulated differentiated THP-1 cellsen_US
dc.typeThesis/Dissertationen_US
etd.degree.nameDoctor of Science in Dentistryen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineOral Biologyen_US
etd.degree.grantorBoston Universityen_US


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