title: Thymus peptides regulate activity of RAW 264.7 macrophage cells: inhibitory analysis and a role of signal cascades.
abstract: OBJECTIVE
  The aim of this study was to reveal T-lymphocyte-independent mechanisms of thymic peptide-mediated immunomodulation.
  
  
  METHODS
  The effects of two thymic peptides- thymulin and thymopentin were studied in cultured RAW 264.7 macrophages (lipopolysaccharide-stimulated or unstimulated) by measuring cytokine production and signal protein levels.
  
  
  RESULTS
  Both peptides increased proinflammatory cytokine secretion by unstimulated RAW 264.7 macrophages and these effects were blocked by the NF-κB cascade inhibitor, stress-activated protein kinase (SAPK)/JNK cascade inhibitor and, to a lesser extent, Toll-like 4 receptor activity inhibitor. In macrophages stimulated by bacterial lipopolysaccharide, peptides alone did not affect cytokine secretion, but significantly enhanced effects of each of the inhibitors. Thymopentin increased activation of both NF-κB and SAPK/JNK cascades in unstimulated macrophages, while thymulin significantly decreased activation of the SAPK/JNK but not NF-κB cascade in LPS-stimulated macrophages. Thymulin and thymopentin increased production of the heat shock protein HSP72 both in LPS-stimulated and unstimulated cells.
  
  
  CONCLUSIONS
  Thymulin and thymopentin are effective anti-inflammatory modulators with direct actions on innate immune cells; the effects involve multiple signal cascades, including NF-κB and SAPK/JNK pathways. Since signaling cascades are now considered to be targets for new therapies, thymic peptides may be prospective modulators of signaling cascades, acting alone or in combination with other agents.
authors.affiliation: Institute of Cell Biophysics of Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Institutskaya Street, Russia. lunin@pochta.ru
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Lunin
authors.forename: Olga V
authors.initials: OV
authors.lastname: Glushkova
authors.forename: Maxim O
authors.initials: MO
authors.lastname: Khrenov
authors.forename: Svetlana B
authors.initials: SB
authors.lastname: Parfenyuk
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Novoselova
authors.forename: Evgeny E
authors.initials: EE
authors.lastname: Fesenko
authors.forename: Elena G
authors.initials: EG
authors.lastname: Novoselova
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D056747:Immunomodulation; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013935:Thymic Factor, Circulating / Q000494:pharmacology*; D016305:Thymopentin / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors
chemical_list: D000873:Anthracenes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013449:Sulfonamides; D051197:Toll-Like Receptor 4; C507035:ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate; C432165:pyrazolanthrone; D013935:Thymic Factor, Circulating; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D016305:Thymopentin