Figure 7.

This figure shows how JNK may interact with neurons and microglia through cytokines and transcription factors. JNK controls inflammatory mediators such as IL-1B, TNF-α, iNOS, and NO (126–128). Activated JNK has been involved with cytokine, oxidative species, and transcription factors. TNF-α stimulates JNK, which in turn stimulates ROS. However, ROS may in turn stimulate JNK. It is known that TNF-α stimulating JNK would result in neuronal apoptosis. Moreover, NF-kB when stimulated by TNF would inhibit ROS (127). An aromatic herb, lindera neesiana kurz (LNE), used as an anti-inflammatory substance, reduces pro-inflammatory expression in LPS stimulated microglia cells, such as JNK, p-38, NO, iNOS, COX-2 production and pro-inflammatory cytokine related neuronal injury to JNK phosphorylation in microglia cells (116, 129) and suggested that JNK activation, triggers pro-inflammatory mediators such as TNF-α, IL-6, IL-1β, COX-2, iNOS, NO and PGE₂, and transcription factors such as AP-1 and NF-κB. SP600125 is a JNK inhibitor which inhibits COX-2 activity through IL-1B. Conversely, IL-1B induces both COX-2 and JNK activation (126). This makes IL-1B a main target for JNK. JNK inhibition has also been observed to increase anti-inflammatory markers (116), which may restore the inflammatory imbalance observed in flush response and prevent microglial activated neuronal death (130).