Figure 7. The role of enteric glia in inflammation – feed‐forward loop leading to increased cell death.

Both ATP and nitric oxide (NO) released from enteric glia regulate normal gut physiology (see text for details). Infection‐induced TLR signalling increases iNOS expression via NF‐κB and results in increased release of NO, a molecule with an antimicrobial effect. Excessive NO release, either by the infection or by other inflammatory signals (omitted for clarity) can also damage the cells leading to a surge of purines and S100β. While S100β enhances NO release via the increased iNOS expression, purine signalling increases intracellular calcium concentration ([Ca²⁺]_i) and increased ATP release via Cx43 hemichannels. Increased [Ca²⁺] can also lead to increased iNOS activity and expression via CaMKII and PKC, respectively. Both PKC and CaMKII were not directly investigated in enteric glia (light grey); our findings indirectly show that PKC does not play a role in enteric glia (dashed arrows). The main findings are summarized from Esposito et al. (2014), Turco et al. (2014) and Brown et al. (2015); see text for details. Abbreviations: CaMKII, Ca²⁺/calmodulin‐dependent protein kinase II; eNTPDase, ecto‐nucleoside triphosphate diphosphohydrolase; iNOS, inducible nitric oxide synthase; NF‐κB, nuclear factor kappa‐light‐chain‐enhancer of activated B cells; PKC, protein kinase C; PLC, phospholipase C; PPARα, peroxisome‐proliferator‐activated receptor‐α; S100β, S100 calcium‐binding protein β; TLR, toll‐like receptor.