The immunoblot analysis further validated the histological finding of reduced levels of several cell cycle and oncogenic pathway signaling proteins such as TGFβ, SMAD4, KRAS, p53, pERK, p-EGFR, and VEGF in the anti–IL-18–pretreated cerulein-with-AOM–treated mice compared to the those without anti–IL-18 pretreatment (Fig 5H). This evidence concerns the gene SMAD4 and infectious otitis media.