title: Differential inflammatory responses triggered by toxic small molecules.
abstract: OBJECTIVE
  The aim of this study is to determine whether exposure to hazardous chemicals alters chemokine or cytokine production in macrophages and link these events to changes in intracellular signaling pathways and activation of specific gene promoters.
  
  
  METHODS
  RAW 264.7 mouse macrophages were treated with selected toxic industrial chemicals (TICs) and examined for changes in immune function. Luminex multiplex technology was used to assess changes in cytokine/chemokine expression and activation of kinase signaling pathways. In addition, a panel of macrophage cell lines with promoter-specific luciferase reporter genes were generated and treated with the TICs, and transcriptional responses to these chemicals were detected by changes in luminescence.
  
  
  RESULTS
  Changes in expression of cytokines and chemokines were linked to changes in the activation state of intracellular signaling pathways. Overall, the findings reveal that sublytic levels of TICs can alter the profile of cytokines and chemokines expressed by macrophages, with a pattern that suggests immunosuppression. The data demonstrate that critical changes in immune function correlate with activation of kinase signaling pathways in macrophages.
  
  
  CONCLUSIONS
  These data provide insight into the effects of sublytic doses of selected TICs on macrophage function, with a particular emphasis on identifying changes in expression of cytokines and chemokines. These altered patterns in immune function were linked to changes in the activation state of intracellular signaling pathways. The data strongly suggest that small amounts of TICs can have subtle, yet very critical, effects on macrophages.
authors: Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. sbarua@ouhsc.edu
authors: Soumitra
authors: S
authors: Barua
authors: Jason
authors: J
authors: Larabee
authors: James L
authors: JL
authors: Regens
authors: Jimmy D
authors: JD
authors: Ballard
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D018925:Chemokines / Q000378:metabolism; D002712:Chlorides / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D017930:Genes, Reporter / Q000187:drug effects; D015386:Hazardous Substances / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D009994:Osmolar Concentration; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013457:Sulfur Compounds / Q000737:chemistry / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018925:Chemokines; D002712:Chlorides; D016207:Cytokines; D015386:Hazardous Substances; D006843:Hydrocarbons, Chlorinated; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D013457:Sulfur Compounds