Cervical Cancer induces NLRP3 inflammasome activation in human peripheral blood monocytes

Abstract

Abstract Background Chronic inflammation plays an important role in tumorigenesis of HPV-associated cervical cancer (CC). However the role of inflammasome on CC has not been yet elucidated. Aim To investigate the interplay between inflammasome and CC to determine the contribution of inflammasome activation in the progression of CC. Methods Inflammasome activation was analyzed in SiHa, Caski, C33 cells lines in monolayer and spheroids cultures representing the CC model. The cell lines was also co-cultured with human monocytes isolated from Healthy donors (HD). Peripheral blood mononuclear cells (PBMC) of patients with CC or precursor lesions (CIN) were also stimulated to evaluate inflammasome activation. Results The co-culture of CC cell lines and monocytes induced an increased production of IL-1ß in spheroids model. The culture with the specific NLRP3 inhibitor (MCC-950) showed that the IL-1ß is derived from monocytes through NLRP3 receptor activation. These results indicated that CC is able to activate NLRP3 inflammasome and IL-1ß production in monocytes, however how it happens it still remains unclear. CC conditioned medium was not able to activate monocytes suggesting that possibly a physical interaction between cancer cells and monocytes is needed. Moreover whether IL-1ß production is beneficial or not for the tumor control is still debated. IL-1ß production is higher in LPS-induced CC PBMC than in CIN PBMC. Conclusion Our finds suggests that CC is able to activate NLRP3 inflammasome and IL-1ß production in monocytes, and IL-1ß production is higher in patients with CC.