title: Effects of tumour necrosis factor alpha (TNFalpha) on Mytilus haemocytes: role of stress-activated mitogen-activated protein kinases (MAPKs).
abstract: BACKGROUND
  Many studies indicate that innate immunity in invertebrates can be modulated by a cytokine network like in vertebrates. In molluscs, the immune response is carried out by circulating haemocytes and soluble haemolymph factors. In the present study, the effects of heterologous TNFalpha (tumour necrosis factor alpha) on cell signalling and function in the haemocytes of the bivalve Mytilus galloprovincialis Lam. were investigated.
  
  
  CONCLUSIONS
  Addition of TNFalpha in the absence of haemolymph serum [in ASW (artificial sea water)] induced cellular stress, as indicated by lysosomal destabilization, and decreased phagocytosis; on the other hand, in the presence of serum, TNFalpha did not affect lysosomal stability and even stimulated phagocytosis. TNFalpha induced rapid phosphorylation of the stress-activated p38 and JNK (c-Jun N-terminal kinase) MAPKs (mitogen-activated protein kinases); both effects were persistent in ASW but transient in serum. Activation of p38 and JNKs in mediating the effects of TNFalpha was confirmed by the use of specific MAPK inhibitors. Moreover, flow cytometric analysis indicated that TNFalpha in the presence of serum induced transient phosphatidylserine exposure on the haemocyte surface, evaluated as annexin V binding; in ASW, the cytokine resulted in a stable increase in the percentage of both annexin- and propidium iodide-positive cells, indicating possible apoptotic/necrotic processes. The results indicate that TNFalpha can affect the function of bivalve haemocytes through conserved transduction pathways involving stress-activated MAPKs and suggest that the haemocyte response to the cytokine is influenced by soluble haemolymph components.
authors.affiliation: Istituto di Scienze Fisiologiche, Università di Urbino Carlo Bo, Loc. Crocicchia, 61029 Urbino (PU), Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Betti
authors.forename: Caterina
authors.initials: C
authors.lastname: Ciacci
authors.forename: Lucia C
authors.initials: LC
authors.lastname: Lorusso
authors.forename: Barbara
authors.initials: B
authors.lastname: Canonico
authors.forename: Tania
authors.initials: T
authors.lastname: Falcioni
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gallo
authors.forename: Laura
authors.initials: L
authors.lastname: Canesi
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation; D005434:Flow Cytometry; D006434:Hemocytes / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D049878:Mytilus; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases