title: Immunoregulatory potential of marine algal toxins yessotoxin and okadaic acid in mouse T lymphocyte cell line EL-4.
abstract: We have studied the effects of the marine algal toxins yessotoxin (YTX) and okadaic acid (OA) on the T cell receptor complex (TCR) expression, an important mechanism by which T cell responsiveness is controlled. Immune system cells are relevant targets to study the immunoregulatory potential of marine toxins since the immune system has been reported as one of the targets of marine algal toxins. This study reports results from exposing the mouse T lymphocyte cell line EL-4 to increasing concentrations of YTX and OA for 72h. We found that both YTX and OA affected TCR recycling kinetics and induced a specific and reversible TCR down-regulation in T lymphocyte EL-4 cells that was time and concentration dependent. Experiments using the potent protein kinase C (PKC) inhibitor stausporine indicated that YTX-induced TCR down-regulation was partially mediated by PKC activation. In contrast, OA-induced TCR down-regulation was mediated by the serine/threonine protein phophatase 2A (PP2A) inhibition. In summary, the results suggest that OA and YTX concentrations in a similar range than those detected in mice bloodstream after oral administration have the potential to adjust the T cell responsiveness during the initiation of T cell activation by affecting the TCR expression levels via PKC and PP2A activities.
authors.affiliation: Department of Chemical Engineering, University of Almería, Almería, Spain. alicia@ual.es
authors.forename: Alicia Martín
authors.initials: AM
authors.lastname: López
authors.forename: Juan J Gallardo
authors.initials: JJ
authors.lastname: Rodríguez
authors.forename: Asterio Sánchez
authors.initials: AS
authors.lastname: Mirón
authors.forename: Francisco García
authors.initials: FG
authors.lastname: Camacho
authors.forename: Emilio Molina
authors.initials: EM
authors.lastname: Grima
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017252:CD3 Complex / Q000096:biosynthesis; D002460:Cell Line; D005434:Flow Cytometry; D051379:Mice; D008978:Mollusk Venoms; D019319:Okadaic Acid / Q000494:pharmacology*; D035964:Oxocins / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects / Q000502:physiology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D000276:Adjuvants, Immunologic; D017252:CD3 Complex; D008978:Mollusk Venoms; D035964:Oxocins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D019319:Okadaic Acid; D011493:Protein Kinase C; D019311:Staurosporine; C066632:yessotoxin