Fosfomycin, an antibiotic, possessed TGF-beta-like immunoregulatory activities.
The regulatory effects of fosfomycin (FOM) were correlated closely with the multifunction of TGF-beta in the modulation of immune responses in vivo and in vitro. LPS-induced polyclonal IgM and IgG antibody responses were depressed at 3 days after the initial culture and subsequently enhanced at day 10 by FOM or TGF-beta. Neither FOM nor TGF-beta inhibited LPS-induced IgA antibody responses, whereas dexamethasone (DX) reduced polyclonal IgM, IgG and IgA antibody responses wholly. The suppression of antibody responses and Mv1Lu cell proliferation induced by FOM or TGF-beta was partly overcome with soluble TFG-beta receptors (sRIII). Oral, i.v. and i.p. administration of FOM exhibited similar enhanced SRBC-specific antibody responses to that seen after oral administration of TGF-beta. The addition of FOM and latent TGF-beta inhibited the proliferation of Mv1Lu cells, but FOM did not lead to an increase in plasmin activities, which convert latent to active TGF-beta, and further the expression of TGF-beta receptors on the cell surface. In addition, FOM failed to enhance TGF-beta secretion. These findings suggest that immunomodulation of FOM results in increased sensitivity of cells to TGF-beta.
Ishizaka
S
S
Department of Parasitology, Nara Medical University, Kashihara, Japan.
Takeuchi
H
H
Kimoto
M
M
Kanda
S
S
Saito
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D005578:Fosfomycin / Q000494:pharmacology*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008907:Mink; D011509:Proteoglycans / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan; D005578:Fosfomycin; D005341:Fibrinolysin