Nrf2 promotes MWCNT-induced pulmonary inflammation in mice

Multi-walled carbon nanotubes (MWCNTs) are used to reinforce plastics, but recent studies have demonstrated that exposure to MWCNTs via inhalation or intratracheal instillation induced lung cancer in rats. The present study was designed to determine the role of nuclear factor erythroid 2-related factor (Nrf2) in MWCNT-induced inflammatory response in the lung of mice. Anesthetized male Nrf2 null mice and age-matched wild-type mice were exposed once to MWCNTs at either 0, 10, or 20 µg/mouse by pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected after 7 days to evaluate pulmonary inflammation. Exposure to MWCNTs significantly increased BALF total cell counts and total protein level in wild-type mice, but not in Nrf2 null mice. MWCNT-exposed wild-type mice showed the significant increases in interleukin (IL)-1β, IL-6, and keratinocyte-derived chemokines (KC) levels in BALF, but these were not seen in BALF of Nrf2 null mice. Exposure to MWCNTs at 10 and 20 μg/mouse for 7 days did not significantly increase oxidative stress in both genotypes, but exposure to MWCNTs increased the levels of IL-1β and caspase-1 only in the lungs of wild-type mice. Our results demonstrate that Nrf2 promotes MWCNT-induced pulmonary inflammation, probably through inflammasome activation.