Proposed model for the involvement of NF-κB signaling in the regulation of cytokine and chemokine in Tat±morphine treated astrocytes.

<p>Arrows indicate activation of the signaling pathway; the “┤” signs indicate pathway inhibition. Exposure to Tat alone increases IκB phosphorylation/degradation and NF-κB transcriptional activity, and additionally increases [Ca²⁺]_i in astrocytes <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004093#pone.0004093-Haughey1" target="_blank">[48]</a>. Although morphine treatment alone fails to significantly activate NF-κB in astrocytes, in combination with Tat it can potentiate Tat-induced increases in [Ca²⁺]_i at sites upstream of NF-κB <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004093#pone.0004093-Hauser2" target="_blank">[37]</a>. How [Ca²⁺]_i affects IκB degradation in the present study is uncertain (?), but may involve increased oxidative stress <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004093#pone.0004093-Sen1" target="_blank">[55]</a>, and decreased proteasome activity.