To heal or not to heal? Chemokines as determinants of constructive or destructive inflammatory microenvironments

To heal or not to heal? Chemokines as determinants of constructive or destructive inflammatory microenvironments Dear Readers, Dental pulp stem cells gained attention as a subpopulation of postnatal stem cells with the ability of multipotential differentiation. Therefore, these cells, specifically SHED (stem cells from human exfoliated deciduous teeth), have been extensively investigated as a potential cellular source to clinical regenerative intervention 12. Despite the buzz generated by the potential 'external' tissue engineering (and tooth-engineering) application of dental pulp stem cells, its 'intrinsic' role in dental pulp and periapical tissues repair also have been investigated 6. In this context, dental pulp stem cells are supposed to be recruited and activated upon pulp hypoxia, injury and infection, and initially would participate in reparative host response 3. The initial pulp response to injury is characterized by the classic inflammatory vascular and cellular events, being Gram-negative bacteria and their products (such as LPS) described to be a major trigger of host response in pulp environment. Interestingly, endodontic infections associated with Gram-negative Enterococcus faecalis induce pulp cells to produce the chemokine CXCL12 (also called SDF-1, stromal cell-derived factor-1) 10. CXCL12 is considered the major chemoattractant factor for the stem cells, whose effect is mediated by its binding to the receptor CXCR4, characteristically expressed by and a marker of stem cells populations 5. The role of CXCL12-CXCR4 axis in stem cells mobilization was demonstrated in different experimental models, and its modulation was proposed to be a useful therapeutic strategy aiming tissue repair and regeneration. It is important to consider that stem cells mobilization (similarly to inflammatory cell migration) is dependent on inflammation-induced adhesion molecules and chemokines, which characterize a 'constructive' inflammation setting, or, in other words, reinforce the involvement of certain inflammatory mediators in repair process 1. However, considering that CXCL12 is observed in both inflamed pulpal and periapical tissues 9 , why noxious stimuli of such tissues leading to a subsequent inflammation not always evolve to a successful tissue repair outcome? In this issue of the JAOS, Sipert, et al. 11 (2013) describes that while both permanent and deciduous teeth derived dental pulp fibroblasts produce CXCL12 upon LPS stimulation, a simultaneous production of the chemokine CCL3 was also observed. However, while a minor impact in CXCL12 production is described, a clear increase in CCL3 production was observed. Conversely to CXCL12, CCL3 (also called MIP-1α-macrophage inflammatory protein-1 alpha) is a prominent inflammatory chemokine 7. CCL3 is …