Decreased content of the IL1α processing enzyme calpain in murine bone marrow-derived macrophages after treatment with the benzene metabolite hydroquinone

Abstract

Benzene is an important industrial chemical known to produce hematotoxicity in mice and humans. Hydroquinone, a major metabolite of benzene, inhibits conversion of the precursor form of IL 1α (pre-IL1α) to IL 1α in murine bone marrow-derived macrophages in vitro, and a similar effect can be demonstrated in vivo after treatment of mice with benzene. The protease which converts pre-ILla to IL1α is calpain. We examined decreases in calpain content in bone marrow-derived macrophages as a possible mechanism underlying hydroquinoneinduced decreases in pre-IL1α conversion. Hydroquinone, at concentrations which were not overtly cytotoxic, decreased total calpain activity in macrophages by 10–30%. Using immunoblot analysis macrophage calpain II levels were shown to be decreased by approximately 50% after treatment with hydroquinone. Under the same conditions, no changes were observed in calpain I content using immunoblot analysis. These data show that decreased calpain II content represents a potential mechanism of hydroquinone-induced inhibition of preILla processing, and may contribute to benzene-induced alterations in bone marrow stromal cell function and myelotoxicity.