Immunomodulation by 17beta-estradiol in bivalve hemocytes.
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 17beta-estradiol (E(2)) has been shown to affect neuroimmune functions. We have investigated the immunomodulatory role of E(2) in Mytilus hemocytes, the cells responsible for the innate immune response. E(2) at 5-25 nM rapidly stimulated phagocytosis and oxyradical production in vitro; higher concentrations of E(2) inhibited phagocytosis. E(2)-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 O(2)(-); NO production was confirmed by nitrite accumulation. The effects of E(2) were prevented by the antiestrogen tamoxifen and by specific kinase inhibitors, indicating a receptor-mediated mechanism and involvement of p38 MAPK and PKC. E(2) 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-alpha- and -beta-like proteins in hemocytes was investigated by immunofluorescence confocal microscopy. The effects of E(2) on immune function were also investigated in vivo at 6 and 24 h in hemocytes of E(2)-injected mussels. E(2) significantly affected hemocyte lysosomal membrane stability, phagocytosis, and extracellular release of hydrolytic enzymes: lower concentrations of E(2) resulted in immunostimulation, and higher concentrations were inhibitory. Our data indicate that the physiological role of E(2) in immunomodulation is conserved from invertebrates to mammals.
Canesi
Laura
L
Istituto di Scienze Fisiologiche, Università Carlo Bo di Urbino, Italy. Laura.Canesi@unige.it
Ciacci
Caterina
C
Lorusso
Lucia Cecilia
LC
Betti
Michele
M
Guarnieri
Tiziana
T
Tavolari
Simona
S
Gallo
Gabriella
G
D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006434:Hemocytes / Q000187:drug effects* / Q000276:immunology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D049878:Mytilus / Q000201:enzymology* / Q000276:immunology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011960:Receptors, Estrogen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D050882:CREB-Binding Protein; D011493:Protein Kinase C; D020929:Mitogen-Activated Protein Kinase Kinases