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Editorial
. 2022 Apr 1;205(7):740-742.
doi: 10.1164/rccm.202201-0008ED.

The P2X7 Receptor in Cystic Fibrosis Monocytes: Linking CFTR Deficiency to Inflammation

André M Cantin  1   2
Affiliations
Editorial

The P2X7 Receptor in Cystic Fibrosis Monocytes: Linking CFTR Deficiency to Inflammation

André M Cantin. Am J Respir Crit Care Med. .
No abstract available

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Figures

Figure 1.
Figure 1.
Monocyte P2X7 receptor signaling and nucleotide-binding oligomerization domain, leucine-rich repeat–containing protein 3 (NLRP3) inflammasome activation. LPS binding to Toll-like receptor 4 (TLR4) induces pro–IL-1β synthesis and NLRP3 inflammasome assembly. Hypoxia and/or cell lysis induces the release of a large amount of extracellular ATP (eATP) through Panx1, which engages the P2X7 receptor. In contrast to macrophages, monocytes alone can also release sufficient eATP to activate the NLRP3 inflammasome. Cation influx drives K+ efflux either through P2X7 or alternate channels, a key step in initiating NLRP3 inflammasome activation. Upon activation, the NLRP3 inflammasome converts pro–caspase-1 to caspase-1, which acts upon pro–IL-1β to produce IL-1β. Other effects of P2X7 engagement with eATP include a macropore formation that contributes to apoptosis and pyroptosis, T-helper cell type 17 (Th17) development, an increase in mitochondrial calcium, and modulation of several transcription factors that affect inflammation. Restoration of cystic fibrosis transmembrane conductance regulator (CFTR) function normalizes Cl− and P2X7-dependent K+ efflux, inhibits inflammasome activation, and decreases IL-1β release in CF monocytes. Several P2X7 inhibitors have been identified. AP-1 = adaptor protein complex 1; CREB = cAMP-responsible element-binding protein; HIF-1 = hypoxia-inducible factor-1; NF-κB = nuclear factor-κB.
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References

    1. Chen G, Sun L, Kato T, Okuda K, Martino MB, Abzhanova A, et al. IL-1β dominates the promucin secretory cytokine profile in cystic fibrosis. J Clin Invest . 2019;129:4433–4450. - PMC - PubMed
    1. Sly PD, Gangell CL, Chen L, Ware RS, Ranganathan S, Mott LS, et al. AREST CF Investigators Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med . 2013;368:1963–1970. - PubMed
    1. Montgomery ST, Dittrich AS, Garratt LW, Turkovic L, Frey DL, Stick SM, et al. AREST CF Interleukin-1 is associated with inflammation and structural lung disease in young children with cystic fibrosis. J Cyst Fibros . 2018;17:715–722. - PubMed
    1. Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DW. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med . 1995;151:1075–1082. - PubMed
    1. DeBoer EM, Kimbell JS, Pickett K, Hatch JE, Akers K, Brinton J, et al. AREST CF Lung inflammation and simulated airway resistance in infants with cystic fibrosis. Respir Physiol Neurobiol . 2021;293:103722. - PMC - PubMed

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