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This Article Full Text Full Text (PDF) All Versions of this Article: 291/3/R664    most recent 00139.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Canesi, L. Articles by Gallo, G. Search for Related Content PubMed PubMed Citation Articles by Canesi, L. Articles by Gallo, G.

INFLAMMATION AND CYTOKINES

Immunomodulation by 17-estradiol in bivalve hemocytes

¹Istituto di Scienze Fisiologiche, Università "Carlo Bo" di Urbino, Urbino; ²Cellular Physiology Unit, Department of Experimental Evolutionary Biology, Alma Mater Studiorum, University of Bologna, Bologna; and ³Dipartimento di Biologia, Sezione di Fisiologia, Università di Genova, Genoa, Italy

Submitted 28 February 2006 ; accepted in final form 29 March 2006

In mammals, estrogens have dose- and cell-type-specific effects on immune cells and may act as pro- and anti-inflammatory stimuli, depending on the setting. In the bivalve mollusc Mytilus, the natural estrogen 17-estradiol (E₂) has been shown to affect neuroimmune functions. We have investigated the immunomodulatory role of E₂ in Mytilus hemocytes, the cells responsible for the innate immune response. E₂ at 5–25 nM rapidly stimulated phagocytosis and oxyradical production in vitro; higher concentrations of E₂ inhibited phagocytosis. E₂-induced oxidative burst was prevented by the nitric oxide (NO) synthase inhibitor N^G-monomethyl-L-arginine and superoxide dismutase, indicating involvement of NO and O₂^–; NO production was confirmed by nitrite accumulation. The effects of E₂ were prevented by the antiestrogen tamoxifen and by specific kinase inhibitors, indicating a receptor-mediated mechanism and involvement of p38 MAPK and PKC. E₂ induced rapid and transient increases in the phosphorylation state of PKC, as well as of a aCREB-like (cAMP responsive element binding protein) transcription factor, as indicated by Western blot analysis with specific anti-phospho-antibodies. Localization of estrogen receptor-- and --like proteins in hemocytes was investigated by immunofluorescence confocal microscopy. The effects of E₂ on immune function were also investigated in vivo at 6 and 24 h in hemocytes of E₂-injected mussels. E₂ significantly affected hemocyte lysosomal membrane stability, phagocytosis, and extracellular release of hydrolytic enzymes: lower concentrations of E₂ resulted in immunostimulation, and higher concentrations were inhibitory. Our data indicate that the physiological role of E₂ in immunomodulation is conserved from invertebrates to mammals.

estrogen; innate immunity; kinase-mediated cell signaling; Mytilus