Project description:Staphylococcus aureus lipoteichoic acid (aLTA) and Lactobacillus plantarum LTA (pLTA) engage the same Toll-like receptor 2 (TLR2) signaling pathway, but exert different effects on the innate immune/inflammatory responses. aLTA is the leading cause of gram-positive bacterial sepsis induced by S. aureus, whereas pLTA is considered as a promising therapeutic agent for pathogen-induced septic shock. The mechanisms underlying the different functions of aLTA and pLTA remain unclear. We used human oligo microarrays to investigate the transcriptomes of human THP-1 monocytes upon exposure to aLTA and pLTA. Differential gene expression profiles were observed between the aLTA- and pLTA-treated cells. The expression levels of 1301 genes in aLTA-treated cells were changed more than 2 fold. These genes are critically involved in immune/inflammatory responses, cell adhesion, cell signal transduction, transcription factors, anion transport, proteolysis and oxidative processes. Especially, a variety of genes that encode cytokines/chemokines and other related molecules such as those belonging to the IRAK, TRAF, NF-κB, and STAT families were remarkably up-regulated by aLTA stimulation. In contrast, the expression levels of only 93 genes were altered by more than 1.5 fold in pLTA-treated cells, and these genes are almost not correlative with immune/inflammatory responses and other related processes compared with those of aLTA-treated cells. The different functions of aLTA and pLTA were further compared with the differential expressions of a selected group of genes, i.e., IRAKs, TRAFs and some cytokines/chemokines through RT-PCR and ELISA assays. The gene expression of IRAK2 could be markedly induced by aLTA, but significantly inhibited by pLTA treatment. These results suggest that the different functions of aLTA and pLTA on innate immunity and inflammation might be due to their different effects on the expression of some genes related with the innate immune/inflammatory responses, such as IRAK2 etc.

Project description:Staphylococcus aureus lipoteichoic acid (aLTA) and Lactobacillus plantarum LTA (pLTA) engage the same Toll-like receptor 2 (TLR2) signaling pathway, but exert different effects on the innate immune/inflammatory responses. aLTA is the leading cause of gram-positive bacterial sepsis induced by S. aureus, whereas pLTA is considered as a promising therapeutic agent for pathogen-induced septic shock. The mechanisms underlying the different functions of aLTA and pLTA remain unclear. We used human oligo microarrays to investigate the transcriptomes of human THP-1 monocytes upon exposure to aLTA and pLTA. Differential gene expression profiles were observed between the aLTA- and pLTA-treated cells. The expression levels of 1301 genes in aLTA-treated cells were changed more than 2 fold. These genes are critically involved in immune/inflammatory responses, cell adhesion, cell signal transduction, transcription factors, anion transport, proteolysis and oxidative processes. Especially, a variety of genes that encode cytokines/chemokines and other related molecules such as those belonging to the IRAK, TRAF, NF-κB, and STAT families were remarkably up-regulated by aLTA stimulation. In contrast, the expression levels of only 93 genes were altered by more than 1.5 fold in pLTA-treated cells, and these genes are almost not correlative with immune/inflammatory responses and other related processes compared with those of aLTA-treated cells. The different functions of aLTA and pLTA were further compared with the differential expressions of a selected group of genes, i.e., IRAKs, TRAFs and some cytokines/chemokines through RT-PCR and ELISA assays. The gene expression of IRAK2 could be markedly induced by aLTA, but significantly inhibited by pLTA treatment. These results suggest that the different functions of aLTA and pLTA on innate immunity and inflammation might be due to their different effects on the expression of some genes related with the innate immune/inflammatory responses, such as IRAK2 etc. We analyzed gene expression change by aLTA and pLTA in THP1 cell to find the active pathway and related biology function.

Project description:Acute Respiratory Distress Syndrome (ARDS)/ Acute Lung Injury (ALI) is a syndrome defined by the presence of acute hypoxemic respiratory failure, bilateral pulmonary infiltrates on chest radiograph, a known clinical risk factor (e.g. sepsis, pneumonia, trauma, gastric fluid aspiration, pancreatitis, massive transfusion), and the absence of physiologic or clinical evidence of congestive heart failure. The Identification of SNPs Predisposing to Altered ALI Risk (iSPAAR) study is a multi-institutional cooperative study, funded through the NHLBI Recovery Act, that assembled samples and phenotype information from existing cohorts. The consortium included samples from patients with ARDS from the NIH NHLBI ARDS Clinical Trials Network (ARDSNet). Samples were obtained from 3 interventional treatment trials in patients with ARDS, including the Fluid and Catheter Treatment Trial (FACTT), the Albuterol to Treat Acute Lung Injury (ALTA) trial, and the Omega-3 Fatty Acid/Antioxidant Supplementation for ALI trial (Omega). In addition to ARDSnet samples, samples from the other cohorts included cases of established ARDS but also controls: critically ill patients who were at-risk for ARDS but who did not develop ARDS during their hospital course. These cohorts included the Molecular Epidemiology of Acute Respiratory Distress (MEA) Study enrolled at the Harvard University/Massachusetts General Hospital, the Systemic Inflammatory Immune Response Syndrome (SIRS) Patient Database and ICU Traumatic Injury cohorts from Harborview Medical Center, and cohorts collected from the ALI research programs at the University of Pennsylvania and the University of California, San Francisco. The Cohort is utilized in the following dbGaP sub-studies. To view genotypes, other molecular data, and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" box located on the right hand side of this top-level study page <a href="study.cgi?study_id=phs000631">phs000631</a> ARDSnet iSPAAR Consortium. <ul> <li><a href="study.cgi?study_id=phs000334">phs000334</a> ESP_LungGO_ALI </li> <li><a href="study.cgi?study_id=phs000686">phs000686</a> ALI_GeneticRisk </li> </ul>

Dataset Information

Acute Respiratory Distress Network (ARDSNet) Studies 06 and 08 Prospective, Randomized, Multicenter Trial of Aerosolized Albuterol Versus Placebo for the Treatment of Acute Lung Injury (ALTA) (ARDSNet-ALTA-BioLINCC)

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