Reproduction de : Thèse de doctorat : Pharmacie. Immunologie : Reims : 2007. / Titre provenant de l'écran-titre. Bibliographie f.102-146.

Tie-2 expressing monocytes (TEMs) were identified to be a subset of monocytes that was potent inducer of tumor angiogenesis in various types of cancer. On the other hand, monocytes and macrophages are crucially involved in the innate immune response, but the function of TEMs in this process is not well understood. Therefore, we studied the role of Tie-2 in regulating the inflammatory response initiated by lipopolysaccharide in murine macrophages. First, we observed that a small percentage of bone marrow-derived macrophages express Tie-2. Furthermore, we observed that Tie-2 ligands were able to induce phosphorylation of signalling proteins in macrophages. However, we found that Tie-2 ligands were not able to regulate pro-inflammatory cytokine secretion, nor were the ligands able to prevent apoptosis induced by lipopolysaccharide in macrophages. These results suggest that contrary to current evidence in the literature, Tie-2 ligands may not play a role in modulating the pro-inflammatory response in TEMs.

Tie-2 expressing monocytes (TEMs) were identified to be a subset of monocytes that was potent inducer of tumor angiogenesis in various types of cancer. On the other hand, monocytes and macrophages are crucially involved in the innate immune response, but the function of TEMs in this process is not well understood. Therefore, we studied the role of Tie-2 in regulating the inflammatory response initiated by lipopolysaccharide in murine macrophages. First, we observed that a small percentage of bone marrow-derived macrophages express Tie-2. Furthermore, we observed that Tie-2 ligands were able to induce phosphorylation of signalling proteins in macrophages. However, we found that Tie-2 ligands were not able to regulate pro-inflammatory cytokine secretion, nor were the ligands able to prevent apoptosis induced by lipopolysaccharide in macrophages. These results suggest that contrary to current evidence in the literature, Tie-2 ligands may not play a role in modulating the pro-inflammatory response in TEMs.

No description available.

Monocytic cells survive HIV replication and consequent cytopathic effects because of their decreased sensitivity to HIV-induced apoptosis. However, the mechanism underlying this resistance to apoptosis remains poorly understood. I hypothesized that exposure to microbial products, translocated from the gut, may confer anti-apoptotic properties in human monocytic cells through interaction with their corresponding Toll-like receptors (TLRs). Using HIV-Vpr(52-96) peptide as a model apoptosis-inducing agent, I demonstrated that unlike monocyte-derived macrophages, undifferentiated primary human monocytes and pro-monocytic THP-1 cells are highly susceptible to Vpr(52-96)-induced apoptosis. Interestingly, monocytes and THP-1 cells stimulated with TLR-9 agonists, CpG and E.coli DNA, induced almost complete resistance to Vpr(52-96)-induced apoptosis albiet via a TLR-9 independent signaling pathway. Moreover, CpG and E.coli DNA selectively induced the anti- apoptotic Inhibitor of Apoptosis Protein-2 (c-IAP-2) and inhibition of the c-IAP-2 gene by either specific siRNAs or synthetic second mitochondrial activator of caspases (Smac) mimetic reversed CpG-induced resistance against Vpr(52-96)-mediated apoptosis. I demonstrated that c-IAP-2 was regulated by the c-Jun N terminal kinase (JNK) and the calcium signaling pathway in particular the calmodulin-dependent protein kinase-II (CaMK-II). Furthermore, inhibition of JNK and the calcium signaling including CaMK-II by either pharmacological inhibitors or their specific siRNAs reversed CpG-induced protection against Vpr(52-96)-mediated apoptosis. I also showed that CpG-induced JNK phosphorylation through activation of calcium signaling pathway.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 6 uppsatser.

Thesis (Ph.D.)--University of Western Australia, 2005.

Thesis (M.Sc. (Clinical Pathology))--Mahidol University, 1986.

Thesis (Ph. D.)--University of Canterbury, 2008. / Typescript (photocopy). Includes bibliographical references (p. 211-250). Also available via the World Wide Web.