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Activation of the Adipose Tissue NLRP3 Inflammasome Pathway in Cancer Cachexia

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de Jesus, Joyce de Cassia Rosa [1] ; Murari, Ariene Soares de Pinho [1] ; Radloff, Katrin [1] ; de Moraes, Ruan Carlos Macedo [1] ; Figueredo, Raquel Galvao [1] ; Pessoa, Ana Flavia Marcal [1] ; Rosa-Neto, Jose Cesar [2] ; Matos-Neto, Emidio Marques [1] ; Alcantara, Paulo S. M. [3] ; Tokeshi, Flavio [3] ; Maximiano, Linda Ferreira [3] ; Bin, Fang Chia [4] ; Formiga, Fernanda Bellotti [4] ; Otoch, Jose P. [1, 3] ; Seelaender, Marilia [1]
Número total de Autores: 15
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Med, Dept Surg, Canc Metab Res Grp, Lab Invest Med LIM26, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Immunometab Lab, Sao Paulo - Brazil
[3] Univ Sao Paulo, Dept Surg Clin, Univ Hosp, Sao Paulo - Brazil
[4] Santa Casa Sao Paulo, Dept Coloproctol, Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN IMMUNOLOGY; v. 12, SEP 23 2021.
Citações Web of Science: 0

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-1 beta and IL-18.</p> 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-kappa B.</p> Results For CC we found opposite modulation in ScAT and PtAT for the gene expression of TLR4, Caspase-1 (cachectic group) and for NF-kappa B p50, NF-kappa B p65, IL-1 beta. 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-1 beta and IL-18 protein content in ScAT supernatant was decreased in the WSC and CC as compared to CTL explants.</p> 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.</p> (AU)

Processo FAPESP: 12/50079-0 - Inflamação sistêmica em pacientes com caquexia associada ao câncer: mecanismos e estratégias terapêuticas, uma abordagem em medicina translacional
Beneficiário:Marilia Cerqueira Leite Seelaender
Modalidade de apoio: Auxílio à Pesquisa - Temático