ENDOGENOUS CYTOKINE EXPRESSION PROFILES IN RETINOIC ACID-INDUCED IGA PRODUCTION BY LPS-STIMULATED MURINE SPLENOCYTES

AU-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 ki netics of expression of various cytokine mRNAs were analyzed by the RT -PCR method. RA induced the expression of IL-5 and TGF-beta 2 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-beta 1 and TGF-beta 3 mRNAs were constitutively expressed in both culture groups. RA enhanced IgA production by LPS-stimulated s pleen cells but not that by LPS-stimulated mu(+) naive splenic B-cells . For RA-induced IgA production, the B-cells required T-cells or the c ulture 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-beta-neutralizing antibodies. These findings sug gest that RA induces IgA production by (IL-5 + LPS)-stimulated B-cells in TGF-beta-independent and TGF-beta-dependent manners. (C) 1995 Acad emic Press Inc.