Rubratoxin B induces interleukin-6 secretion in mouse white adipose tissues and 3T3-L1 adipocytes

Abstract

Rubratoxin B is a mycotoxin that causes hepatic fatty changes. We examined whether white adipose tissue (WAT) contributes to rubratoxin B toxicity through effects on interleukin (IL)-6. Rubratoxin B was intraperitoneally injected into mice at 1.5 mg/kg. Urinary albumin and macrophage inflammatory protein (MIP)-2 secretion were increased 24 h after treatment with rubratoxin B. Rubratoxin B was previously reported to induce IL-6 secretion, although the secreting tissue was unknown. Here, rubratoxin B prominently augmented IL-6 transcription in epididymal WAT and to a lesser extent in perirenal WAT and liver. Rubratoxin B may thus exert its toxicity partly through IL-6 secretion from WATs. In contrast, MIP-2 gene expression increased only in liver. To examine the specific involvement of adipocytes, we used mouse 3T3-L1 cells, an in vitro differentiation model of adipocytes. Expression of IL-6 and MIP-2 mRNA in 3T3-L1 adipocytes after 24 h of rubratoxin B treatment increased dose-dependently. Rubratoxin B also increased IL-6 and MIP-2 secretion from 3T3-L1 adipocytes. The increase in IL-6 secretion was markedly higher than the increase in IL-6 gene transcription, indicating that rubratoxin B-induced secretion of IL-6 from 3T3-L1 adipocytes is chiefly controlled post-transcriptionally. Rubratoxin B is thus the first mycotoxin known to exert its toxicity through effects on WATs.