ABSTRACT
Burkholderia pseudomallei is the causative agent of melioidosis and represents a potential bioterrorism threat. In this study, the transcriptomic responses of B. pseudomallei infection of a human macrophage cell model were investigated using whole-genome microarrays. Gene expression profiles were compared between infected THP-1 human monocytic leukemia cells with or without treatment with Daboia russelli russelli daboiatoxin (DRRDbTx) or ceftazidime (antibiotic control). Microarray analyses of infected and treated cells revealed differential upregulation of various inflammatory genes such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX-2), vascular endothelial growth factor (VEGF), chemokine C-X-C motif ligand 4 (CXCL4), transcription factor p65 (NF-kB); and several genes involved in immune and stress responses, cell cycle, and lipid metabolism. Moreover, following DRR-DbTx treatment of infected cells, there was enhanced expression of the tolllike receptor 2 (TLR-2) mediated signaling pathway involved in recognition and initiation of acute inflammatory responses. Importantly, we observed that highly inflammatory cytokine gene responses were similar in infected cells exposed to DRR-DbTx or ceftazidime after 24 h. Additionally, there were increased transcripts associated with cell death by caspase activation that can promote host tissue injury. In summary, the transcriptional responses during B. pseudomallei infection of macrophages highlight a broad range of innate immune mechanisms that are activated within 24 h post-infection. These data provide insights into the transcriptomic kinetics following DRR-DbTx treatment of human macrophages infected with B. pseudomallei.
Subject(s)
Burkholderia pseudomallei/drug effects , Gene Expression Regulation/drug effects , Macrophages/drug effects , Proteins/pharmacology , Transcriptome , Viper Venoms/chemistry , Animals , Burkholderia pseudomallei/growth & development , Burkholderia pseudomallei/ultrastructure , Ceftazidime/pharmacology , Cell Line , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Gene Expression Profiling , Genome-Wide Association Study , Host-Pathogen Interactions , Humans , Interleukin-1/genetics , Interleukin-1/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Macrophages/metabolism , Macrophages/microbiology , Macrophages/ultrastructure , Microarray Analysis , NF-kappa B/genetics , NF-kappa B/metabolism , Platelet Factor 4/genetics , Platelet Factor 4/metabolism , Proteins/isolation & purification , Signal Transduction , Toll-Like Receptor 2/genetics , Toll-Like Receptor 2/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , ViperidaeABSTRACT
Contrast-induced nephropathy is well-known sequelae of iodinated contrast (diatrizoate meglumine). Carbon dioxide (CO(2)) can be used as an alternative contrast agent. The aim of this study was to compare the renal injury and the quality of images of aortogram using iodinated contrast versus CO(2) using digital subtraction angiography (DSA). This prospective randomized study was done in 29 healthy dogs using DSA aortogram. Dogs were randomly assigned to receive iodinated contrast or CO(2). 6-F pigtail catheter was introduced via femoral artery approach to perform aortogram under general anesthesia. Serum creatinine (S.Cr.) and urinary enzymes, namely: N-acetyl D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and gamma glutamyl transferase (GGT), were measured before and 48 hours after aortogram. There was no change in S.Cr. in both the groups. Significantly more enzymuria was seen following iodinated contrast than CO(2). Enzymuria pre and postaortogram following the iodinated contrast was GGT: 14.9 +/- 5.92 vs. 26.2 +/- 15.1 (P = 0.001), NAG: 1.63 +/- 0.90 vs. 3.6 +/- 2.14 (P = 0.0001), and AAP: 1.51 +/- 0.75 vs. 3.38 2.41 (P = 0.001), and in the CO(2) group was GGT: 15.5 +/- 4.9 vs. 21.1 +/- 9.04 (P = 0.02), NAG: 2.12 +/- 1.06 vs. 3.82 3.27 (P = 0.08), and AAP: 1.28 +/- 0.76 vs. 2.51 +/- 1.72 (P = 0.03). More than 50% increase over the preprocedural value was significantly less following CO(2). Images obtained with iodinated contrast were superior to those with CO(2,) however, the quality of image with CO(2) was adequate for delineation of the renal artery and major branches. Both iodinated contrast and CO(2) cause significant enzymuria. More severe enzymuria (>50% increase) was seen significantly less with the use of CO(2). Quality of images is better with iodinated contrast.
