Inflammasome Activation Is Critical to the Protective Immune Response during Chemically Induced Squamous Cell CarcinomaReportar como inadecuado




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Chronic inflammation affects most stages of tumorigenesis, including initiation, promotion, malignant differentiation, invasion and metastasis. Inflammasomes have been described as involved with persistent inflammation and are known to exert both pro and antitumour effects. We evaluated the influence of apoptosis-associated speck-like protein containing a caspase recruitment domain ASC and caspase CASP-1 in the antitumor immune response using a multistage model of squamous cell carcinoma SCC development. Absence of ASC and CASP-1 resulted in an earlier incidence and increased number of papilloma. Loss of inflammassome function in mice resulted in decreased presence of natural killer NK, dendritic DC, CD4+, CD8+ and CD45RB+ T cells in the tumor lesions as well as in lymph nodes LN compared with WT mice. Increased percentage of CD4+CD25+Foxp3+ T cells was associated with association with inflammasome loss of function. Moreover, significant differences were also found with neutrophils and macrophage infiltrating the lesions. Myeloperoxidase MPO, but not elastase ELA, activity oscillated among the groups during the SCC development. Levels of proinflammatory cytokines IL-1β, IL-18, Tumor Necrosis Factor TNF-α and Interferon IFN-γ were decreased in the tumor microenvironment in the absence of inflammasome proteins. These observations suggest a link between inflammasome function and SCC tumorigenesis, indicating an important role for inflammasome activation in the control of SCC development.



Autor: Thais Helena Gasparoto, Carine Ervolino de Oliveira, Luisa Thomazini de Freitas, Claudia Ramos Pinheiro, Juliana Issa Hori, Gusta

Fuente: http://plos.srce.hr/



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