PMC:2817507 / 15746-17947 JSONTXT

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Activation of TLR4 stimulates IκBα phosphorylation and degradation, resulting in nuclear translocation of NFκB, which initiates transcription of genes associated with innate immune responses and inflammation [5, 6]. We observed that the levels of phosphorylation of IκB and the activity of NFκB were significantly increased in brain tissue after ICH. The temporal profile of the expression of p-IκB and the activation of NFκB was similar to that of the expression of TLR4. Our data suggest that ICH stimulates activation of the TLR4/NFκB signaling pathway, which is consistent with previous reports that activation of NFκB is regulated through the TLR4-mediated signaling pathway. TLR4 plays an important role in the recognition of microbial components [19, 20] and can also recognize endogenous molecules such as the degradation products of macromolecules, products of proteolytic cascades, intracellular components of ruptured cells, and products of genes that are activated by inflammation. For instance, HSP70, HSP32, HSP27, and enzymes involved in oxidative stress are found to be upregulated in the brain after ICH, which may be produced by injured neuronal cells or blood cells [21]. It may be speculated that these molecules produced in damaged brain or came from blood cells and constituents of plasma server as endogenous TLR4 ligands, activate TLR4-mediated NFκB signaling, and initiate the inflammatory responses in IHC brain. However, the specific endogenous ligands for TLR4 in hemorrhagic brain have not been determined and need to be identified through further 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