Tesis doctoral de Ferdinand Noukwe Noukwe
We organized the thesis into two chapters: chapter i: to evaluate the synergic effect of il-12/il-18 and m-csf/gm-csf on monocytes differentiation and their impact on the respiratory burst and cholesterol metabolism of monocytes-derived macrophages, monocytes were differentiated for 7 days in the presence of both granulocyte-macrophage colony-stimulating factor (gm-csf) and macrophage colony-stimulating factor (m-csf) or interleukin-12 (il-12) and il-18 to produce respectively m/gm-macrophages and il12/il18-macrophages. As control, monocytes were differentiated only with m-csf, gm-csf, il-12 and il-18 to produce respectively m-macrophages, gm-macrophages, il12-macrophages and il18-macrophages. Samples analyses of four monocytes donors demonstrated a differential in the cholesterol metabolism and respiratory burst of macrophage subpopulations. Stimulated m/gm-macrophages and il12/il18-macrophages produce high level of h2o2 and myeloperoxidase; and generate significant amount of hocl in response to pma. In contrast, they show low levels of anti-oxidant enzyme catalase. Moreover they intensify ldl oxidation and spontaneously accumulate significant amount of cholesterol when incubated with unmodified low-density lipoprotein. the results suggest that m-csf/gm-csf or il12/il18 pathways might be some critical synergic signals experienced by monocytes/macrophages during their differentiation in-vivo; in which their atherogenic potential or their capacity to oxidize ldl increase. chapter ii: recent studies show that hiv-1 load rebound after long periods of treatment interruptions (ti), results in a burst of coronary artery disease (cad) biomarkers. We investigate whether short interruptions induce a burst of these biomarkers, whether their levels return to the baseline during treatment resumption and if the burst were related to the number of interruptions. Cad biomarkers crp, cxcl8, d-dimer, mmp-9 and plasma lipids were measured from stored plasma samples of 21 chronically hiv-1 infected subjects enrolled in a study evaluating six cycles of «2 weeks off / 4 weeks on» antiretroviral therapy. Subjects were clustered into those with a viral load rebound after stopping treatment and those without. The levels of crp, mmp-9, cxcl8, d-dimer and triglycerides rose significantly after each ti in subjects with viral load rebound. Changes of means increment in subjects without viral load rebound were too low relative to the baseline and without clinical interest as values stayed between the normal plasma ranges. No times effect was observed during ti except for crp. All biomarkers return to baseline levels after each treatment resumption. the results suggest that antiretroviral ti as short as two weeks are associated with a clinically relevant burst of acute cad biomarkers, that indicating the importance of adhering to treatment.
Datos académicos de la tesis doctoral «Il-12/il-18 and m-csf/gm-csf trigger two new pathways of pro-oxidants enzymes up-regulation on macrophages. an increase in viral load during treatment interruptions induces a burst of factors implicated in cardiovascular diseases.«
- Título de la tesis: Il-12/il-18 and m-csf/gm-csf trigger two new pathways of pro-oxidants enzymes up-regulation on macrophages. an increase in viral load during treatment interruptions induces a burst of factors implicated in cardiovascular diseases.
- Autor: Ferdinand Noukwe Noukwe
- Universidad: Autónoma de barcelona
- Fecha de lectura de la tesis: 20/07/2011
Dirección y tribunal
- Director de la tesis
- Margarita Bofill Soliguer
- Tribunal
- Presidente del tribunal: eva Martínez cáceres
- Julián Miguel Blanco arbués (vocal)
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