SKW-6.4 CELL-DIFFERENTIATION INDUCED BY INTERLEUKIN-6 IS STIMULATED BY BUTYRATE

We investigated if sodium butyrate (NaBu), an inhibitor of histone dea cetylase, and its analogs modulate cytokine-induced differentiation of the human B cell line SKW 6.4 transformed by the Epstein-Barr virus. NaBu markedly enhanced interleukin (IL)-6-induced IgM production with an accompanying increase in the level of histone H4 acetylation and au gmented IgM production induced by IL-4 and phorbol 12-myristate 13-ace tate. From both the enhancing effect of cell differentiation and the e ffect of inducing histone hyperacetylation in SKW 6.4 cells, other his tone deacetylase inhibitors and NaBu analogs were divided into three g roups: those that increased both IL-6-induced antibody production and histone acetylation, those that caused histone hyperacetylation, but f ailed to induce the differentiation, and those that were ineffective a t inducing either activity. No agent that enhanced IgM production with out inducing histone hyperacetylation was found among the inhibitors a nd analogs we tested. These results suggest that the increase in the h istone acetylation is necessary, but it is insufficient to augment dif ferentiation of SKW 6.4 cells. Thus another activity of NaBu in additi on to the inhibition of histone deacetylase may be involved in promoti ng IL-6-induced differentiation. Our results also suggest that fatty a cids that have a straight chain of four carbon atoms or are branched w ith four and five carbon atoms, which contain no hydrophilic substitue nts, or those with similar structures, show this other activity. (C) 1 998 Elsevier Science B.V. All rights reserved.