JNK signaling is required for the MIP-1α-associated regulation of Kupffer cells in the heat stroke response

Severe heat stroke (HS) consists of extreme hyperthermia with thermoregulatory failure, leading to high morbidity and mortality. Liver injury is a complication of HS that is associated with inflammatory responses and Kupffer cells (KCs), which are resident macrophages in the liver that serve as a major source of inflammatory cytokines; however, the association and the underlying mechanisms of KC functions in HS-induced endotoxemia and inflammation require an improved understanding. The important chemokine macrophage inflammatory protein-1α (MIP-1α) increases inflammatory responses and the secretion of inflammatory molecules from KCs, including tumor necrosis factor-α, interleukin (IL)-1β and IL-6. In addition, the activation of c-Jun N-terminal kinase (JNK) signaling is responsible for the development of liver inflammation. Therefore, HS animal and cell models were constructed in order to investigate the pathways involved in the HS-induced dysfunction of KCs. The results of the present study suggest that JNK may be involved in the MIP-1α-associated pathogenesis of KCs in HS injury.