Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice

摘要: The FDA-approved small-molecule drug ibrutinib is an effective targeted therapy for patients with chronic lymphocytic leukemia (CLL). Ibrutinib inhibits Bruton’s tyrosine kinase (BTK), a involved in B cell receptor signaling. However, the potential regulation of neuroinflammatory responses brain by has not been comprehensively examined. BV2 microglial cells were treated (1 μM) or vehicle (1% DMSO), followed lipopolysaccharide (LPS; 1 μg/ml) PBS. RT-PCR, immunocytochemistry, and subcellular fractionation performed to examine effects on responses. In addition, wild-type mice sequentially injected (10 mg/kg, i.p.) (10% DMSO, i.p.), LPS PBS, astrocyte activations assessed using immunohistochemistry. significantly reduced LPS-induced increases proinflammatory cytokine levels primary but astrocytes. regulated TLR4 signaling alter levels. decreased p-AKT p-STAT3 levels, suggesting that attenuates inhibiting AKT/STAT3 pathways. Interestingly, also migration AKT Moreover, ibrutinib-injected exhibited microglial/astrocyte activation COX-2 IL-1β Our data provide insights mechanisms therapeutic strategy neuroinflammation-related diseases.