Isothiocyanates inhibit psoriasis-related proinflammatory factors in human skin

Abstract

4-Methylthiobutylisothiocyanate (MTBI), the main rocket (Eruca sativa) seed isothiocyanate (ITC), and its oxidized form, sulforaphane (SFN), were assessed for their potential effects on psoriasis-related factors. MTBI and SFN were evaluated for their effect on mRNA expression and cytokine secretion in vitro in human monocytes and macrophage-like cells and ex vivo in topically treated inflamed human skin. In addition, they were assayed in vivo for morphological changes in topically treated psoriasiform human skin in severe-combined immunodeficient (SCID) mice. MTBI and SFN contributed to the prevention of inflammation development and reduced ongoing inflammation by downregulating lipopolysaccharide (LPS)-induced mRNA expression of the psoriasis-related cytokines, interleukin (IL)-12/23p40 (25-58%), tumor necrosis factor (TNF)-α (15-37%) and IL-6 (25-71%), in human macrophage-like cells. In monocytes, they tended to act additively on cytokine mRNA and reduced IL-12/23p40 (51%) secretion. In an ex-vivo inflamed human skin organ culture, MTBI (1μg/ml) reduced the secretion of IL-1 (39%) and IL-6 (32%). Moreover, 2/8 and 3/8 of the MTBI- and SFN-treated psoriasiform SCID mice, respectively, recovered partially or entirely from the psoriasiform process. Results from these models indicate the potential of rocket seed ITCs as biological agents in the therapy of psoriasis and inflammation-related skin diseases.