No description available.

Objective: Study the effects of vitamin D on viral driven innate immune responses, by looking at differences in cytokine production, receptor expression, and endogenous vitamin D levels. Methods: Primary peripheral blood mononuclear cells (PBMC) and epithelial cells (EC) were cultured in the presence of viral ligands and vitamin D. Enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) were used to determine cytokine production and mRNA expression. Results: PBMC stimulated with toll-like receptor 4 ligand (TLR4L), but not viral TLR8L, led to decreased pro- and anti-inflammatory cytokine production in the presence of 1,25(OH)2D3. RIG-like receptor (RLR) activation, on the other hand, in primary EC exhibited decreased pro-inflammatory cytokine production in the presence of vitamin D. Conclusions: Our findings are among the first to show differences between bacterial and viral driven innate immune responses in the presence of vitamin D. As responsiveness in RLR activated primary EC was altered in the presence of vitamin D, our data reveal the importance of studying the immune system as a whole.

The macrophage (Mφ) foam cell in the atherosclerotic plaque microenvironment is subjected to cytokines and growth factors secreted by smooth muscle cells (SMCs), endothelial cells (ECs), platelets and lesional Mφ themselves. This thesis examines the effects of some of these soluble factors on a murine macrophage membrane molecule, the macrophage scavenger receptor (MSR), considered pivotal in foam cell formation and atherogenesis. Macrophage Colony-stimulating factor (MCSF) enhances MSR expression and functional activity (including MSR-dependent adhesion) in elicited peritoneal Mφ markedly and selectively. The T lymphocyte products, Th1 (interferon-gamma(IFN-γ)) and Th2 (chiefly interleukin-4 (IL-4)) cytokines, have divergent effects with IL-4 upregulating and IFN-γ either maintaining or downregulating MSR status. IL-4 induced MSR microheterogeneity is due to changes in N-linked glycosylation, specifically sialylation and may be physiologically significant. In contrast to interleukin-10 (IL-10), transforming growth factor-beta (TGF-β) inhibits MSR upregulation, also when produced endogenously. TGF-β is as potent an inhibitor of MSR function as M-CSF is a stimulator. A cleaved truncated soluble form of MSR which lacks the cytoplasmic domain is present, by immunochemical assays, in culture supernatants. M-CSF increases soluble MSR release in vitro which is functionally active. Following upregulation of MSR surface expression in transfected CHO cells by prolonged culture, a modest MSR-dependent contribution to adhesion becomes apparent. To determine a possible adhesionpromoting region in the MSR, the binding site of mAb 2F8 was mapped using a series of MSR truncation mutants, and localized to residues 183 to 197 in the proximal cchelical coiled-coil domain. Morphological evidence, obtained by confocal and electron microscopy, supports an adhesion role for the MSR in primary Mφ and transfected CHO cells. MSR expression is prominently directed to the adherent surface and its distribution is restricted to cellular contact areas with the substratum. Organs and atherosclerotic lesions from mice deficient in M-CSF (osteopetrotic) and apolipoprotein E were examined to determine the effects of M-CSF on Mφ phenotype (including MSR expression) and lesion development in vivo. Though severely hypercholesterolemic, doubly deficient mice are protected against atherosclerosis and exhibit fewer Mφ and low MSR expression on remaining M-CSF independent populations. Prominent hepatic lipid accumulation suggests a crucial M-CSF dependent role for Kupffer cells in lipoprotein uptake, transfer to hepatocytes and biliary excretion of cholesterol. Regulation of MSR activity may therefore be important for the recruitment of Mφ into the arterial wall and, at the post-endothelial stage, to anchor Mφ at specific locations, thus favouring foam cell formation.

No description available.

No description available.

Aims of the research:To characterise the tissue histology and tissue distribution patterns of C. albicans during systemic murine candidiasis.To develop a reliable, reproducible and sensitive SQ-RT-PCR for the quantitation of in vivo cytokine gene transcription.To use this technique to determine the in vivo pattern of tissue specific cytokine gene expression during systemic candidiasis.To determine if cytokine gene expression patterns vary between resistant BALB/c and sensitive CBA/CaH mice during primary systemic candidiasis.To determine if differences in tissue distribution of C. albicans in infected mice is matched by differences in tissue responses to infection.To determine if cytokine mRNA expression patterns during secondary systemic candidiasis, are different to those during primary systemic candidiasis.To determine if cytokine gene expression patterns vary between resistant BALB/c and sensitive CBA/CaH mice during secondary systemic candidiasis.

Thesis (Ph. D.)--George Mason University, 2007. / Title from PDF t.p. (viewed Jan. 18, 2008). Thesis director: Ancha Baranova Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biosciences. Vita: p. 213 Includes bibliographical references (p. 188-212). Also available in print.

Dissertation (Ph.D.)--Auburn University, 2006. / Abstract. Vita. Includes bibliographic references.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 6 uppsatser.

Thesis (Ph.D.)--University of Adelaide, Dept. of Surgery (Neurosurgery) and Institute of Medical and Veterinary Science, Dept. of Neuropathology, 2004. / "June 2004" Bibliography: leaves 218-238.