The Warburg effect promoted the activation of the NLRP3 inflammasome induced by Ni-refining fumes in BEAS-2B cells

Abstract

Nickel (Ni) is a known human carcinogen that has an adverse effect on various human organs in occupational workers during Ni refinement and smelting. In the present study, we used real-time polymerase chain reactions, Western blot analysis, and a lactate production assay to investigate whether an increase in the NLRP3 inflammasome induced by Ni-refining fumes was associated with the Warburg effect in BEAS-2B cells, a nonmalignant pulmonary epithelial line. Exposure to Ni-refining fumes suppressed cell proliferation and increased lactate production compared with those in an untreated control group in a dose- and time-dependent manner. Ni-refining fumes induced the Warburg effect, which was observed based on increases in the levels of hypoxia-inducible factor-1α, hexokinase 2, pyruvate kinase isozyme type M2, and lactate dehydrogenase A. In addition, Ni-refining fumes promoted increased expression of NLRP3 at both the gene and protein levels. Furthermore, inhibition of the Warburg effect by 2-Deoxy-d-glucose reversed the increased expression of NLRP3 induced by Ni-refining fumes. Collectively, our data demonstrated that the Warburg effect can promote the expression of the NLRP3 inflammasome induced by the Ni-refining fumes in BEAS-2B cells. This indicates a new phenomenon in which alterations in energy production in human cells induced by Ni-refining fumes regulate the inflammatory response.

NLRP3 inflammasome activation in response to metals

“…Xin et al found that Ni-refining fume particles can induce the decrease of the mitochondrial membrane potential (MMP) and the increase of the opening rate of the mitochondrial permeability transition pore (MPTP) in human lung epithelial BEAS-2B cells, and activation of the NLRP3 inflammasome induced by Ni-refining fume particles can be significantly suppressed by NAC, an effective ROS remover, suggesting that Ni-refining fume particles activate the NLRP3 inflammasome by causing mitochondrial dysfunction and ROS production (68). Another study also showed that Ni-refining fumes promoted the expression of the NLRP3 inflammasome by inducing the Warburg effect in BEAS-2B cells (69). In addition, it has also been confirmed that activation of the NLRP3 inflammasome by Ni ions is independent of the phagolysosome-cathepsin B pathway (70).…”

Antioxidants and Long Covid

“…TGF-β and the NLRP3(NACHT, LRR and PYD protein 3) in ammasome are connected (62) and both of these are associated with the Warburg e ect (63). The in ammasome is vital to the pathogenesis of ME/CFS(64), FM, Alzheimer's (65), IBD (66,67), autoimmune disease (68,69), EBV (70) and Long Covid (71).…”