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Fig. 3 | Journal of Inflammation

Fig. 3

From: Coupled cell networks are target cells of inflammation, which can spread between different body organs and develop into systemic chronic inflammation

Fig. 3

In cells experiencing inflammation, glutamate release into the extracellular space is increased, and Ca2+ signaling in cellular networks is over-activated. Several receptors are influenced by the increased expression of TLR4, and the responses of other receptors such as P2 and mGluR5 are also changed. The Na+/K+-ATPase is downregulated, the glutamate transporters GLT-1 and GLAST are changed, and actin filaments (white bands disorganized) in the cytoskeleton are reorganized, thereby abolishing the balance between the Ca2+ regulatory processes. This process leads to the down-regulation of intercellular Ca2+ signaling and thereby of Cx43 in gap junctions. ATP is released from the cells and binds to P2 purinoceptors, which generates extracellular Ca2+ oscillations/waves and increased release from internal stores. The increased release of pro-inflammatory cytokines such as IL-1╬▓ occurs extracellularly. The clearing of increased glutamate concentrations from the extracellular space, which plays a critical role in preventing glutamate excitotoxicity, is attenuated. The illustration was created by Pontus Andersson, ArtProduction, Gothenburg, Sweden

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