epidermal-growth-factor and HIV-Infections

Epidermal growth factor (EGF) and Hepatocyte growth factor (HGF) both have tyrosine kinase receptors (EGFR and c-Met) which upon binding, activates and regulates many important cellular processes such as cell survival, growth, proliferation, differentiation, invasion, repair and so forth via the RAS/MAPK/ERK1/2, PI3K/AKT and JAK STAT3 pathways. These processes are crucial for the development of a placenta and other functions in order for a normal pregnancy to occur. Hence, this study determined the concentrations of HGF and EGF to find the correlation between HIV and preeclampsia (PE).. A total sample size of n = 80 was used, n = 40 preeclamptic women and n = 40 normotensive women these were further stratified into HIV-positive and HIV-negative women. Analysis of the growth factors were done by using the multiplex Bio-Plex immunoassay method.. Irrespective of HIV status, based on pregnancy type, EGF in PE women displayed an upregulation compared to normotensive women. However, for HGF no variance was found between pregnancy type. Based on HIV status, regardless of pregnancy type, both HGF and EGF levels were significantly increased in HIV-positive women compared to HIV-negative women. Across all groups for HGF, significant difference was found between HIV-negative normotensive women (lower) vs HIV-positive normotensive women (higher). Nevertheless, for EGF across all groups, a statistically significant decrease was found in HIV-negative normotensive women compared to HIV-positive normotensive women, HIV-positive PE women and HIV-negative PE women.. The study demonstrates that there is a strong association between HIV and PE and that HGF and EGF are promising biomarkers to use as a diagnostic tool for PE.

Topics: Adolescent; Adult; Biomarkers; Epidermal Growth Factor; Female; Hepatocyte Growth Factor; HIV Infections; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious; Retrospective Studies; Young Adult

Human immunodeficiency virus (HIV)-infected children are at risk of developing several types of renal diseases, including HIV-associated nephropathy (HIVAN), which is usually seen during late stages of infection in children with a high viral load. This disease is defined by the presence of proteinuria associated with mesangial hyperplasia and/or global-focal segmental glomerulosclerosis combined with microcystic transformation of the renal tubules. Because HIVAN can have an insidious clinical onset, renal biopsy is the only definitive way of establishing a diagnosis. Given the risk of performing this procedure in HIV-infected children with other AIDS-defining illness, we sought to identify informative biomarkers such as growth factors in the urine of 55 HIV-infected children that might be predictive of the extent and activity of the renal lesions characteristic of HIVAN. We found that the levels of epidermal growth factor were lower in the urine of children with renal disease, whereas levels of fibroblast growth factor-2 and metalloproteinase-2 were higher as compared with those levels in infected children without renal disease. Similar changes were observed in HIV-Tg26 mice correlating with the progression of renal disease in this model of HIVAN. Our findings suggest that this urinary growth factor profile may be useful in facilitating the diagnosis of HIV-infected children at risk of developing HIVAN when interpreted in the appropriate clinical setting.

Topics: Adolescent; AIDS-Associated Nephropathy; Animals; Biomarkers; Case-Control Studies; Child; Child, Preschool; Epidermal Growth Factor; Fibroblast Growth Factor 2; HIV Infections; Humans; Infant; Intercellular Signaling Peptides and Proteins; Matrix Metalloproteinase 2; Mice; Mice, Transgenic; Predictive Value of Tests; Viral Load

Assessment of cytokines in body fluids or cells provides important information in understanding the disease process and designing treatment strategies. Recent introduction of antibody-based protein arrays have provided investigators simultaneous and specific detection of multiple analytes in a single sample using minimum volumes. In this study, we used a biochip array system capable of measuring 12 cytokines and growth factors (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1alpha, IL-1beta, IFN-gamma, TNF-alpha, monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF)) in HIV patients with immunological and virological discordance (discordant) to find out differences if any, in their plasma cytokine profiles when compared with concordant HIV-infected individuals. A sandwich chemiluminescent assay was performed with plasma specimens of 110 HIV patients (55 discordant, 55 concordant) and 22 normal healthy individuals followed by enzyme-linked immunosorbent assay (ELISA) to the confirm levels of cytokines and growth factors that showed significant differences in the two groups. The discordant HIV patients showed significantly higher levels of plasma VEGF (P = 0.001) and EGF (P = 0.034) levels when compared with concordant patients. Overall, the patients showed significantly higher levels of TNF-alpha, MCP-1 and VEGF when compared with the normal healthy controls (P < 0.05). ELISA for VEGF (P < 0.001) and EGF (P = 0.004) confirmed the comparison obtained with biochip array, between the discordant and concordant patients. The results of cytokine quantitation by biochip array and ELISA confirmed that this technology is not only comparable but also has a good potential in the future applications involving measurement of multiple cytokines with limiting specimens.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antiretroviral Therapy, Highly Active; Cross-Sectional Studies; Cytokines; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; HIV Infections; Humans; Male; Middle Aged; Plasma; Protein Array Analysis; Reference Values; Vascular Endothelial Growth Factors

Human immunodeficiency virus type 1 (HIV-1) and related primate lentiviruses are known to enter the central nervous system (CNS) during the primary phase of infection. Neuroinvasion by simian immunodeficiency virus and simian human immunodeficiency virus (SHIV) is characterized by transient meningitis and astrocytosis. In this report, we used targeted cytokine cDNA arrays to analyze cortical brain tissue from four pig-tailed macaques inoculated for 2 weeks with pathogenic SHIV(50OLNV) and a normal age-matched pig-tailed macaque. Our results revealed that eight genes were significantly upregulated in all four macaques. These included: leukocyte interferon inducible peptide, corticotrophin releasing factor receptor 1, interleukin 6, CDW40 antigen, cysteine-rich fibroblast growth factor, neurotrophin 3, ciliary neurotrophin factor receptor and cripto-1. The upregulation of three of these genes was confirmed by reverse transcriptase PCR (RT-PCR). Since cripto-1 had not been previously identified within specific cell types within the primate central nervous system, we performed immunohistochemical studies, which revealed the presence of cripto-1 in neurons. RT-PCR studies demonstrated that cripto-1 mRNA was widely expressed in the CNS. These results indicate that immunomodulatory genes are upregulated during the primary phase of infection of the central nervous system. Cripto-1, which acts as a survival factor in tumor cells and may be neuroprotective, is expressed in neurons within the CNS and is upregulated during viral invasion.

Topics: Animals; Cerebral Cortex; Cytokines; Disease Models, Animal; Epidermal Growth Factor; Gene Expression Regulation, Viral; GPI-Linked Proteins; HIV Infections; HIV-1; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Macaca; Membrane Glycoproteins; Neoplasm Proteins; Neurons; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Simian Immunodeficiency Virus