The immunomodulatory action of dexamethasone on monoclonal antibody-producing hybridoma cells.
As found in different studies, glucocorticoid hormones (GCs) as well as interleukin-6 (IL-6) are involved in the modulation of protein glycosylation. In this work we have investigated the immunomodulatory effect of dexamethasone by assessing in vitro IgG glycosylation by monoclonal antibody-producing hybridoma cells. As described in myeloma cell lines, cellular viability and proliferation rates of hybridoma 112D5 cells decrease when cultured with dexamethasone during 24 hours, in a dose-dependent way. Moreover, the corticosteroid triggered apoptosis of the hybridoma, which was observed as soon as 4 h after culturing cells in the presence of the drug. In line with these results, after 24 h, dexamethasone induced a drop in the anti-DNP level of antibodies synthesized by hybridoma 112D5. In previous works we described that asymmetric glycosylation of in vitro synthesized IgG correlated with induction of cell damage. Nevertheless, an increase in asymmetric IgG glycosylation was not observed here, but there was a decrease in the proportion of asymmetrically glycosylated IgG synthesized by the hybridoma after a 4-h culture with the drug. Finally, as results from assessing IL-6 production by ELISA, we conclude that the above described effects of dexamethasone on hybridoma 112D5 cells could not be due to the inhibition of IL-6 synthesis exerted by the corticoid but rather to a direct effect of the drug. Monoclonal antibody (MAb) producing hybridomas provide an excellent in vitro model for the study of the molecular mechanisms involved in immunoglobulin glycosylation.
Canellada
Andrea
A
IDEHU-Instituto de Estudios de la Inmunidad Humoral, Cátedra de Immunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4to piso, 1113, Buenos Aires, Argentina. acanell@ffyb.uba.ar
Margni
Ricardo A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000187:drug effects* / Q000276:immunology; D000932:Antiemetics / Q000494:pharmacology*; D002455:Cell Division; D002470:Cell Survival; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006031:Glycosylation / Q000187:drug effects; D006825:Hybridomas / Q000187:drug effects* / Q000276:immunology; D007074:Immunoglobulin G / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice
D000911:Antibodies, Monoclonal; D000932:Antiemetics; D007074:Immunoglobulin G; D015850:Interleukin-6; D003907:Dexamethasone