title: A combined omics study on activated macrophages--enhanced role of STATs in apoptosis, immunity and lipid metabolism.
abstract: BACKGROUND
  Macrophage activation by lipopolysaccharide and adenosine triphosphate (ATP) has been studied extensively because this model system mimics the physiological context of bacterial infection and subsequent inflammatory responses. Previous studies on macrophages elucidated the biological roles of caspase-1 in post-translational activation of interleukin-1β and interleukin-18 in inflammation and apoptosis. However, the results from these studies focused only on a small number of factors. To better understand the host response, we have performed a high-throughput study of Kdo2-lipid A (KLA)-primed macrophages stimulated with ATP.
  
  
  RESULTS
  The study suggests that treating mouse bone marrow-derived macrophages with KLA and ATP produces 'synergistic' effects that are not seen with treatment of KLA or ATP alone. The synergistic regulation of genes related to immunity, apoptosis and lipid metabolism is observed in a time-dependent manner. The synergistic effects are produced by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and activator protein (AP)-1 through regulation of their target cytokines. The synergistically regulated cytokines then activate signal transducer and activator of transcription (STAT) factors that result in enhanced immunity, apoptosis and lipid metabolism; STAT1 enhances immunity by promoting anti-microbial factors; and STAT3 contributes to downregulation of cell cycle and upregulation of apoptosis. STAT1 and STAT3 also regulate glycerolipid and eicosanoid metabolism, respectively. Further, western blot analysis for STAT1 and STAT3 showed that the changes in transcriptomic levels were consistent with their proteomic levels. In summary, this study shows the synergistic interaction between the toll-like receptor and purinergic receptor signaling during macrophage activation on bacterial infection.
  
  
  BACKGROUND
  Time-course data of transcriptomics and lipidomics can be queried or downloaded from http://www.lipidmaps.org.
  
  
  BACKGROUND
  shankar@ucsd.edu.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors: Department of Bioengineering, San Diego Super Computer Center, Department of Cellular and Molecular Medicine and Department of Chemistry and Biochemistry, University of California San Diego, CA 92093, USA.
authors: Ashok Reddy
authors: AR
authors: Dinasarapu
authors: Shakti
authors: S
authors: Gupta
authors: Mano
authors: M
authors: Ram Maurya
authors: Eoin
authors: E
authors: Fahy
authors: Jun
authors: J
authors: Min
authors: Manish
authors: M
authors: Sud
authors: Merril J
authors: MJ
authors: Gersten
authors: Christopher K
authors: CK
authors: Glass
authors: Shankar
authors: S
authors: Subramaniam
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D007109:Immunity / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics*; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000235:genetics*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D040901:Proteomics; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016207:Cytokines; C506188:Kdo2-lipid A; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D051193:Toll-Like Receptors
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