15d-PGJ₂ Induce Phenotypic Shift of Macrophages Mediated by PPAR-γ in TMJ

Objectives: The aim of this study is evaluate if 15d-PGJ₂ induce phenotypic alteration of resident macrophages type M1 to M2 through HO-1 promoting resolution of inflammatory response, and if the 15d-PGJ₂-induced antinociception is mediated by Ca²⁺/calmodulin protein kinase (CaMKII) in the TMJ of rats.
Methods: Male Wistar rats (n=8) were used. Previously, animals were pretreated with intra-articular injection of the recruiter macrophage, thioglycollate (1%/TMJ/day), during three days. After that, animals were treated with carrageenan (100µg/TMJ) or carrageenan with 15d-PGJ₂ (100ng/TMJ).
Results: Analysis by ELISA showed that intra-articular injection of 15d-PGJ₂ increases the release of the activated transcription factor PPAR-gamma (P <0.05: one-way ANOVA, Tukey Test). Analysis of protein kinase expression dependent Ca²⁺/calmodulin showed no difference between the tested groups (P> 0.05: One-way ANOVA, Tukey test). Histological sections of the periarticular tissues treated with immunohistochemistry showed that the treatment with the recruiter of macrophages, thioglycollate, increases the expression of macrophage M1 and treatment with 15d-PGJ₂ increases the expression of macrophage M2, associated positively with increased expression of HO-1.
Conclusions: In conclusion, the peripheral intra-articular injection of 15d-PGJ₂ alters the macrophages phenotype on periarticular tissue by the hemeoxygenase-1 pathway, resulting in a resolution of the inflammatory process induced by carrageenan. However the antinociceptive effect of 15d-PGJ₂ is independent of the Ca²⁺/calmodulin protein kinase (CaMKII). Finally, the present study suggests that macrophages have a key role on the pathogenesis of inflammatory process and the balance between their phenotypes defines the resolution the inflammatory process.