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BIBTEX RIS

Activation of the Adipose Tissue NLRP3 Inflammasome Pathway in Cancer Cachexia

2021; Frontiers Media; Volume: 12; Linguagem: Inglês

10.3389/fimmu.2021.729182

1664-3224

Joyce de Cassia Rosa de Jesus, Ariene Murari Soares de Pinho, Katrin Radloff, Ruan Carlos Macêdo de Moraes, Raquel Galvão Figuerêdo, Ana Flávia Marçal Pessoa, José Cesar Rosa Neto, Emídio Marques de Matos‐Neto, Paulo Sérgio Martins de Alcântara, Flávio Tokeshi, Linda Ferreira Maximiano, Fang Chia Bin, Fernanda Bellotti Formiga, José Pinhata Otoch, Marília Seelaender,

Autoimmune and Inflammatory Disorders Research

Background Cachexia is a paraneoplastic syndrome that accompanies and compromises cancer treatment, especially in advanced stages, affecting the metabolism and function of several organs. The adipose tissue is the first to respond to the presence of the tumor, contributing to the secretion of factors which drive the systemic inflammation, a hallmark of the syndrome. While inflammation is a defensive innate response, the control mechanisms have been reported to be disrupted in cachexia. On the other hand, little is known about the role of NLRP3 inflammasome in this scenario, a multiprotein complex involved in caspase-1 activation and the processing of the cytokines IL-1β and IL-18. Aim based on the evidence from our previous study with a rodent model of cachexia, we examined the activation of the NLRP3 inflammasome pathway in two adipose tissue depots obtained from patients with colorectal cancer and compared with that another inflammatory pathway, NF-κB. Results For CC we found opposite modulation in ScAT and PtAT for the gene expression of TLR4, Caspase-1 (cachectic group) and for NF-κB p50, NF-κB p65, IL-1β. CD36, expression was decreased in both depots while that of NLRP3 and IL-18 was higher in both tissues, as compared with controls and weight stable patients (WSC). Caspase-1 basal protein levels in the ScAT culture supernatant were higher in WSC and (weight stable patients) CC, when compared to controls. Basal ScAT explant culture medium IL-1β and IL-18 protein content in ScAT supernatant was decreased in the WSC and CC as compared to CTL explants. Conclusions The results demonstrate heterogeneous responses in the activation of genes of the NLRP3 inflammasome pathway in the adipose tissue of patients with cancer cachexia, rendering this pathway a potential target for therapy aiming at decreasing chronic inflammation in cancer.