title: Cyclooxygenase-2 inhibition lacks immunomodulatory effects on T cells.
abstract: OBJECTIVE
  In T cells, cyclooxygenase-1 is constitutively expressed, and cyclooxygenase-2 is induced during activation but their functions are not well known. Although exogenous prostaglandins are potent inhibitors of T cell activation, both immunoactivation and immunosuppression have been attributed to cyclooxygenases inhibitors (NSAIDs). Understanding the functions of the cyclooxygenases on T cells is relevant to the therapeutic use of NSAIDs on T cell mediated rheumatic diseases such as rheumatoid arthritis. In this study, we analyze whether cyclooxygenases play a significant role in T cell functions.
  
  
  METHODS
  Activation, proliferation, and Fas induced apoptosis were analyzed in T cells treated with non-selective (indomethacin) or cyclooxygenase-2 selective (dimethyl-furanone) inhibitors. Intracellular peroxidation was studied in activated T cells by dihydrorhodamine 123 fluorescence analysis of cells treated with COX-2 antisense or control oligonucleotides. COX-2 expression was analyzed by RT-PCR analysis.
  
  
  RESULTS
  Our data show that neither non-selective or selective cyclooxygenase-2 inhibition modify T cell activation, proliferation or apoptosis susceptibility. Furthermore, inhibition of cyclooxygenase-2 expression by antisense oligonucleotides lacks significant effects on T lymphocytes and does not modify their peroxydative capacity.
  
  
  CONCLUSIONS
  According to these data, cyclooxygenases do not seem to play a relevant role in T cells functions in vitro. Therefore, the use of either cyclooxygenase-2 selective or non-selective NSAIDs in patients with autoimmune inflammatory diseases is not expected to induce direct immunomodulatory effects through direct effects on T cells.
authors.affiliation: Servicio de Reumatología, Unidad de Investigación, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Rivero
authors.forename: B
authors.initials: B
authors.lastname: Santiago
authors.forename: M
authors.initials: M
authors.lastname: Galindo
authors.forename: M T
authors.initials: MT
authors.lastname: Brehmer
authors.forename: J L
authors.initials: JL
authors.lastname: Pablos
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010545:Peroxides / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D010545:Peroxides; D017382:Reactive Oxygen Species; D019014:fas Receptor; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium