Site-specific variation in the activity of COX-2 alters the pattern of wound healing in the tail and limb of northern house gecko by differentially regulating the expression of local inflammatory mediators.

The role of COX-2 induced PGE in the site-specific regulation of inflammatory mediators that facilitate disparate wound healing in the tail and limb of a lizard was studied by analysing their levels during various stages of healing. The activity of COX-2 and concentration of PGE surged during the early healing phase of tail along with the parallel rise in EP4 receptor. PGE-EP4 interaction is corelated to early resolution (by 3 dpa) of inflammation by rising the antiinflammatory mediator IL-10. This likely causes reduction in proinflammatory mediators viz., iNOS, TNF-α, IL-6, IL-17 and IL-22. Conversely, in the limb, COX-2 derived PGE likely causes rise in inflammation through EP2 receptor-based signalling, as all the proinflammatory mediators stay elevated through the course of healing (till 9 dpa), while expression of IL-10 is reduced. This study brings to light the novel roles of IL-17 and IL-22 in programming wound healing. As IL-17 reduces in tail, IL-22 behaves in reparative way, causing conducive environment for scar-free wound healing. On the contrary, synergic elevation of both IL-17 and Il-22 form a micro-niche suitable for scarred wound healing in limb, thus obliterating its regenerative potential.