title: The effects of retinoic acid on immunoglobulin synthesis: role of interleukin 6.
abstract: Retinoic acid (RA) and its parent compound, retinol (ROH, vitamin A), have been recognized as important immunopotentiating agents. Previous studies from our laboratory have demonstrated that RA can augment formalin-treated Staphylococcus aureus (SAC)-stimulated immunoglobulin (Ig) synthesis of cord blood mononuclear cells (CBMC). To determine the mechanism(s) by which RA modulates Ig synthesis, we studied the effects of RA on B cells and cytokine production. The addition of RA (10(-5) to 10(-10) M) to Epstein-Barr virus (EBV)-transformed B-cell clones derived from either adult or cord blood B cells augmented Ig secretion twofold. In contrast, cell proliferation was inhibited as measured by 3H-thymidine incorporation. We evaluated two cytokines known to be constitutively produced by EBV cell lines, IL-1 and IL-6. While RA had no effect on IL-1 production, IL-6 synthesis was greatly enhanced (20- to 45-fold), which was also reflected by an increase in steady-state mRNA levels for IL-6 but not TNF-alpha or TGF-beta on Northern blot analysis. Polyclonal rabbit anti-IL-6 antibodies were used to block the augmenting effects of RA on Ig synthesis of adenoidal B cells. RA-induced augmentation in IgG and IgA synthesis was blocked 58 and 29%, respectively, by anti-IL-6 antibodies. These studies suggest that the enhancing effects of RA on Ig synthesis are mediated, at least in part, by the autocrine or paracrine effects of IL-6 on B-cell differentiation.
authors: Department of Pediatrics, Children's Hospital of Buffalo, New York 14222, USA.
authors: M
authors: M
authors: Ballow
authors: S
authors: S
authors: Xiang
authors: W
authors: W
authors: Wang
authors: L
authors: L
authors: Brodsky
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects; D002461:Cell Line, Transformed; D002999:Clone Cells; D005312:Fetal Blood; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis*; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000276:immunology / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D007106:Immune Sera; D007136:Immunoglobulins; D015850:Interleukin-6; D012333:RNA, Messenger; D014212:Tretinoin