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[Display omitted] Acetaminophen (APAP) hepatotoxicity is an important cause of acute liver failure, resulting in massive deaths in many developed countries. Currently, the metabolic process of APAP in the body has been well studied. However, the underlying mechanism of APAP-induced liver injury remains elusive. Increasing clinical and experimental evidences indicate that the innate immune responses are involved in the pathogenesis of APAP-induced acute liver injury (AILI), in which immune cells have dual roles of inducing inflammation to exacerbate hepatotoxicity and removing dead cells and debris to help liver regeneration. In this review, we summarize the latest findings of innate immune cells involved in AILI, particularly emphasizing the activation of innate immune cells and their different roles during the injury and repair phases. Moreover, current available treatments are discussed according to the different roles of innate immune cells in the development of AILI. This review aims to update the knowledge about innate immune responses in the pathogenesis of AILI, and provide potential therapeutic interventions for AILI. [ABSTRACT FROM AUTHOR]

[Display omitted] The application of lapatinib, a widely used dual inhibitor of human epidermal growth factor receptor 1 (EGFR/ERBB1) and 2 (HER2/ERBB2), has been seriously limited due to cutaneous toxicity. However, the specific mechanism of lapatinib-induced cutaneous toxicity has not been clarified, leading to the lack of an effective strategy to improve clinical safety. Here, we found that lapatinib could induce mitochondrial dysfunction, lead to DNA damage and ultimately cause apoptosis of keratinocytes. In addition, we found that lapatinib could induce an aberrant immune response and promote the release of inflammatory factors in vitro and in vivo. Mechanistically, downregulated expression of the DNA repair protein HMGB1 played a critical role in these toxic reaction processes. Overexpression of HMGB1 inhibited keratinocyte apoptosis and inflammatory reactions. Therefore, restoring HMGB1 expression might be an effective remedy against lapatinib-induced cutaneous toxicity. Finally, we found that saikosaponin A could significantly rescue the reduced HMGB1 transcription, which could alleviate lapatinib-induced DNA damage, inhibit keratinocyte apoptosis and further prevent the toxicity of lapatinib in mice. Collectively, our study might bring new hope to clinicians and tumor patients and shed new light on the prevention of cutaneous adverse drug reactions induced by EGFR inhibitors. [ABSTRACT FROM AUTHOR]