Microarray Analysis of PBMC after Plasmodium falciparum Infection: Molecular Insights into Disease Pathogenesis

Our laboratory’s previous microarray analysis of subjects with Plasmodium falciparum revealed up-regulation of Toll-like receptor, NF-kB, TNF-α, IFN-γ, IL-1β, p38 MAPK, and MHC molecules. We performed further time-course microarray analysis focusing on malaria pathogenesis by using peripheral leukocytes as a cellular model. We found up-regulation of coagulation-related genes (SERPINB2, thrombomodulin, thrombospondin), heat shock proteins, glycolytic enzymes, glucose transporters, and vacuolar H+-ATPases in acute febrile malaria. In early malaria, prior to detectable parasitemia, CD36 and ICAM1 were up-regulated. During acute malaria, a correlation was observed between IL-1ß and heat shock proteins, suggesting heat shock protein response may be in the febrile response induced by IL-1ß. CD163, a hemoglobin scavenger receptor, was up-regulated in acute malaria to potentially facilitate free hemoglobin up-take by peripheral leukocytes. In acute malaria, high MafB gene expression was negatively correlated with down-regulation of hemoglobin and platelet counts. Consistent with a down-regulation of hemoglobin expression, peripheral RBC counts tended to increase during the acute malaria. In our model, up-regulations of RBC and/or leucocyte binding mediators like CD36, ICAM1, thrombospondin, and thrombomodulin may contribute to the pathogenesis of cerebral malaria. Similarly, up-regulation of genes coding for glycolytic enzymes, glucose transporter and H+-ATPases may contribute to the hypoglycemia and metabolic acidosis frequently observed in seriously ill malaria patients. Overall gender effects on gene expression profiles between male and female subjects were not apparent, except that some hemoglobins were significantly down-regulated in male versus female; suggesting males may be more prone to the development of malaria associate anemia

SARS-CoV Regulates Immune Function-Related Gene Expressions in Human Monocytic Cells

Background: Severe Acute Respiratory Syndrome (SARS) is characterized by acute respiratory distress (ARDS) and pulmonary fibrosis, and the monocyte/macrophage is the key player in the pathogenesis of SARS.
 
Methods: In this study, we compared the transcriptional profiles of SARS coronavirus (SARS-CoV) infected monocytic cells against that infected by coronavirus 229E (CoV-229E). Total RNA was extracted from infected DC-SIGN transfected monocytes (THP-1-DC-SIGN) at 6 and 24 h after infection and the gene expression was profiled by oligonucleotide-based microarray. 

Results: Analysis of immune-related gene expression profiles showed that 24 h after SARS-CoV infection, (i) IFN-alpha/beta-inducible and cathepsin/proteosome genes were down-regulated; (ii) the hypoxia/hyperoxia-related genes were up-regulated; and (iii) the TLR/TLR-signaling, cytokine/cytokine receptor-related, chemokine/chemokine receptor-related, the lysosome-related, MHC/chaperon-related, and fibrosis-related genes were differentially regulated. 

Conclusion: These results elucidate that monocyte/macrophage dysfunction and dysregulation of fibrosis-related genes are two important pathogenic events of SARS. 
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Alzheimer's disease is TH17 related autoimmune disease against misfolded beta amyloid

Alzheimer's disease is a common neurodegenerative disorder. However, its exact etiology is still unknown. There were several mechanisms proposed such as the tau hypothesis and amyloid hypothesis. However, there is evidence challenging the above two hypotheses. Here, I propose the immune-amyloid hypothesis as a mechanism for Alzheimer's disease. Th17 related autoimmunity contributes to the disease pathogenesis. Accumulation of misfolded beta amyloid can trigger heat shock protein which in turn induces TH17 immunity. By microarray analysis of peripheral blood mononuclear cells, there is up-regulation of many TH17 related molecules after Alzheimer's disease. After knowing the exact disease pathogenesis, we can develop new therapeutic strategies to prevent or treat the detrimental disorder

Alzheimer's disease is TH17 related autoimmune disease against misfoded beta amyloid

Alzheimer's disease is a common neurodegenerative disorder. However, its exact etiology is still unknown. There were several mechanisms proposed such as the tau hypothesis and amyloid hypothesis. However, there is evidence challenging the above two hypotheses. Here, I propose the immune-amyloid hypothesis as a mechanism for Alzheimer's disease. Th17 related autoimmunity contributes to the disease pathogenesis. Accumulation of misfolded beta amyloid can trigger heat shock protein which in turn induces TH17 immunity. By microarray analysis of peripheral blood mononuclear cells, there is up-regulation of many TH17 related molecules after Alzheimer's disease. After knowing the exact disease pathogenesis, we can develop new therapeutic strategies to prevent or treat the detrimental disorder