市原 佐保子

A previous study demonstrated that Nrf2, a transcription factor, unexpectedly promoted multi-walled carbon nanotube (MWCNT)-induced lung inflammation in mice. This finding contrasts with the well-established role of Nrf2 in suppressing inflammatory responses induced by environmental chemicals, highlighting a critical knowledge gap. The present study investigated the effect of sulforaphane, a known activator of Nrf2, on MWCNT-induced lung inflammation in mice, in order to better understand the underlying mechanisms of this response. Each of 48 C57BL/6 J male mouse was anesthetized and exposed once via pharyngeal aspiration to MWCNTs (Mitsui-7) at doses of 0, 10, or 20 μg in 40 μl of dispersion medium per mouse and treated thereafter with subcutaneous 25 mg/kg/day sulforaphane or vehicle for 14 days. Bronchoalveolar lavage fluid (BALF) was collected for differential cell counts. Lung tissues were processed for histopathological analysis and quantification of cytokine or chemokine mRNA expression and Nrf2 protein in nuclear extracts. MWCNTs exposure increased lung weight, BALF lymphocytes, and lung IL-6 expression. Sulforaphane attenuated MWCNTs-induced lung weight gain, lymphocytic infiltration, and upregulation of IL-6 expression, but paradoxically enhanced low-dose MWCNT-induced neutrophil infiltration in BALF, MIP-2 expression, and histopathological inflammation scores. These effects were accompanied by increased levels of active Nrf2 protein in nuclear extracts from lung tissue. Overall, the results indicate that sulforaphane suppresses lymphocyte infiltration while promoting neutrophil recruitment in response to low-dose MWCNTs, suggesting a dual effect of sulforaphane on MWCNT-induced lung inflammation mediated through Nrf2 activation.