Participação das moléculas pentraxina 3 e microRNA-135b na inflamação articular induzida por cristais de ácido úrico

Abstract

Gout is a disease caused by the deposition of monosodium urate crystals (MSU) into the joints. IL-1 is the key cytokine in gout, which is produced and released through NLRP3 inflammasome activation that occurs after MSU crystal phagocytosis by resident cells. Although this disease is known many centuries ago, the mechanisms involved in bothrecognition of MSU crystals by phagocytes, which are responsible for activating the inflammatory process, and also in the control of the inflammatory response induced by these crystals are still not completely elucidated. In this study, it was identified two important regulatory molecules in the context of gout: pentraxin 3 (PTX3) and microRNA-135b.Pentraxins are considered the humoral arm of innate immunity and microRNAs are small RNAs responsible for post-transcriptional regulation in the gene expression. The results of this study showed that PTX3 production is increased in both samples from mice submitted to anexperimental model of gout and also in samples from patients with acute gout. Moreover, it was demonstrated that PTX3 is important for the phagocytosis of MSU crystals in both murine and human cells. Mechanistically, this occurs in mice through Fc receptors, mainly FcRIII. These data suggests that PTX3 is an important mediator for triggering the inflammation caused by MSU crystals. Regarding to microRNA-135b, its expression was significantly increased in the context of experimental gout and it was showed that the expression of this microRNA is regulated by IL-1 in macrophages. In addition, it was possible to identify the microRNA-135b as a negative regulator of IL-1 signalling pathway, targeting MyD88 e IL-1RAcP. These data suggest that microRNA-135b is an important molecule in the control of articular inflammation in acute gout. In this way, the identification of these two regulatory molecules of the inflammation induced by MSU crystals help to understand better the nature of gouty arthritis and also open new perspectives of diagnostic and therapy