Stat-6 signaling pathway and not Interleukin-1 mediates multi-walled carbon nanotube-induced lung fibrosis in mice: insights from an adverse outcome pathway framework [IL1-R1_KO]

Five-to-seven week old female wild type C57BL/6 mice (WT) and C57BL/6 mice deficient in IL1-R1 (IL1-R1 KO) were exposed to Mitsui-7, a type of multiwalled nanotube at a dose of 162 µg/mouse by intratracheal administration. Inflammation was assessed 24 h and 28 days following treatment and fibrotic leison was assessed 28 days following treatment. Inflammation was lower in IL1-RI KO mice compared to that observed in the wild type mice at 24h post exposure. This diffrence was no longer observed at 28 days post-exposure. In contrast, STAT6 KO mice showed suppressed inflammation and fibrotic leison at 28 days post-exposure compared to the wild type mice. The results from this study suggest that STAT 6 signaling pathway is essential for multiwalled nanotube induced fibrotic desease. Wild type (WT) C57BL/6 and IL1-R1 KO mice were exposed to Mitsui-7 (multiwalled carbon nanotubes (MWCNT)) at a dose of 162 µg/mouse by intratracheal administration in a 50 µl suspension Tissues were collected 1 and 28 days post-instillation.