Endogenous Cytokine Expression Profiles in Retinoic Acid-Induced IgA Production by LPS-Stimulated Murine Splenocytes

All-trans-retinoic acid (RA) enhances IgA production by LPS-stimulated murine splenocytes. After stimulation by RA and LPS, or by LPS alone, total RNA was extracted from cultured cells on Days 1 to 4, and the kinetics of expression of various cytokine mRNAs were analyzed by the RT-PCR method. RA induced the expression of IL-5 and TGF-β2 mRNAs in the LPS-stimulated cells. In addition, the expression of IL-6 and IL-2 mRNAs was more intensive in RA-stimulated cells than in unstimulated cells. TGF-β1 and TGF-β3 mRNAs were constitutively expressed in both culture groups. RA enhanced IgA production by LPS-stimulated spleen cells but not that by LPS-stimulated μ(+) naive splenic B-cells. For RA-induced IgA production, the B-cells required T-cells or the culture supernatant from RA-stimulated T-cells. Furthermore, exogenous IL-5 replaced the T-cell requirement, at least in part, in RA-induced IgA production by LPS-stimulated B-cells. This reaction was partially inhibited by anti-TGF-β-neutralizing antibodies. These findings suggest that RA induces IgA production by (IL-5 + LPS)-stimulated B-cells in TGF-β-independent and TGF-β-dependent manners.