Extracellular Acidification Augments NLRP3-Mediated Inflammasome Signaling in Macrophages
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Inflammation is a series of host defense processes in response to microbial infection and tissue injury. Inflammatory processes frequently cause extracellular acidification in the inflamed region through increased glycolysis and lactate secretion. Therefore, the immune cells infiltrating the inflamed region encounter an acidic microenvironment. Extracellular acidosis can modulate the innate immune response of macrophages; however, its role for inflammasome signaling still remains elusive. In the present study, we demonstrated that macrophages exposed to an acidic microenvironment exhibited enhanced caspase-1 processing and IL-1β secretion compared with those under physiological pH. Moreover, exposure to an acidic pH increased the ability of macrophages to assemble the NLR family pyrin domain containing 3 (NLRP3) inflammasome in response to an NLRP3 agonist. This acidosis-mediated augmentation of NLRP3 inflammasome activation occurred in bone marrow-derived macrophages but not in bone marrow-derived neutrophils. Notably, exposure to an acidic environment caused a reduction in the intracellular pH of macrophages but not neutrophils. Concordantly, macrophages, but not neutrophils, exhibited NLRP3 agonist-mediated translocation of chloride intracellular channel protein 1 (CLIC1) into their plasma membranes under an acidic microenvironment. Collectively, our results demonstrate that extracellular acidosis during inflammation can increase the sensitivity of NLRP3 inflammasome formation and activation in a CLIC1-dependent manner. Thus, CLIC1 may be a potential therapeutic target for NLRP3 inflammasome-mediated pathological conditions.
Abstract
Inflammation is a series of host defense processes in response to microbial infection and tissue injury. Inflammatory processes frequently cause extracellular acidification in the inflamed region through increased glycolysis and lactate secretion. Therefore, the immune cells infiltrating the inflamed region encounter an acidic microenvironment. Extracellular acidosis can modulate the innate immune response of macrophages; however, its role for inflammasome signaling still remains elusive. In the present study, we demonstrated that macrophages exposed to an acidic microenvironment exhibited enhanced caspase-1 processing and IL-1β secretion compared with those under physiological pH. Moreover, exposure to an acidic pH increased the ability of macrophages to assemble the NLR family pyrin domain containing 3 (NLRP3) inflammasome in response to an NLRP3 agonist. This acidosis-mediated augmentation of NLRP3 inflammasome activation occurred in bone marrow-derived macrophages but not in bone marrow-derived neutrophils. Notably, exposure to an acidic environment caused a reduction in the intracellular pH of macrophages but not neutrophils. Concordantly, macrophages, but not neutrophils, exhibited NLRP3 agonist-mediated translocation of chloride intracellular channel protein 1 (CLIC1) into their plasma membranes under an acidic microenvironment. Collectively, our results demonstrate that extracellular acidosis during inflammation can increase the sensitivity of NLRP3 inflammasome formation and activation in a CLIC1-dependent manner. Thus, CLIC1 may be a potential therapeutic target for NLRP3 inflammasome-mediated pathological conditions.
참고문헌 (38)
- Rathinam VA, "Inflammasome, inflammation, and tissue homeostasis", Trends Mol Med, 24, pp.304~318 (2018)
- Dubos RJ, "The micro-environment of inflammation or Metchnikoff revisited", Lancet, 269, pp.1~5 (1955)
- Edlow DW, "The pH of inflammatory exudates", Proc Soc Exp Biol Med, 137, pp.1328~1332 (1971)
- Menkin V, "Studies on inflammation : Xiii. Carbohydrate metabolism, local acidosis, and the cytological picture in inflammation", Am J Pathol, 13, pp.25~44 (1937)
- Ricciardolo FL, "Acid stress in the pathology of asthma", J Allergy Clin Immunol, 113, pp.610~619 (2004)
- Simmen HP, "Analysis of pH, pO2 and pCO2 in drainage fluid allows for rapid detection of infectious complications during the follow-up period after abdominal surgery", Infection, 22, pp.386~389 (1994)
- Nedergaard M, "Dynamics of interstitial and intracellular pH in evolving brain infarct", Am J Physiol, 260, pp.R581~R588 (1991)
- Treuhaft PS, "Synovial fluid pH, lactate, oxygen and carbon dioxide partial pressure in various joint diseases", Arthritis Rheum, 14, pp.475~484 (1971)
- Erra Díaz F, "Unravelling the interplay between extracellular acidosis and immune cells", Mediators Inflamm, 2018, pp.1218297~ (2018)
- Casey JR, "Sensors and regulators of intracellular pH", Nat Rev Mol Cell Biol, 11, pp.50~61 (2010)
- Bellocq A, "Low environmental pH is responsible for the induction of nitric-oxide synthase in macrophages. Evidence for involvement of nuclear factor-kappaB activation", J Biol Chem, 273, pp.5086~5092 (1998)
- El-Kenawi AE, "Abstract 3213 : extracellular acidosis alters polarization of macrophages", Cancer Res, 75(Suppl 15), pp.3213~3213 (2015)
- Gabig TG, "Effects of oxygen tension and pH on the respiratory burst of human neutrophils", Blood, 53, pp.1133~1139 (1979)
- Faucher N, "Relationship between pH, sodium, and shape changes in chemotactic-factor-stimulated human neutrophils", J Cell Physiol, 132, pp.483~491 (1987)
- Schroder K, "The inflammasomes", Cell, 140, pp.821~832 (2010)
- 박철호, "Inflammasome-Dependent Peroxiredoxin 2 Secretion Induces the Classical Complement Pathway Activation", Immune Network, 21(5), pp.1~16 (2021), 대한면역학회[DOI]
- Je-Wook Yu, "Mitochondria and the NLRP3 inflammasome: physiological and pathological relevance", Archives of Pharmacal Research, 39(11), pp.1503~1518 (2016), 대한약학회
- Swanson KV, "The NLRP3 inflammasome : molecular activation and regulation to therapeutics", Nat Rev Immunol, 19, pp.477~489 (2019)
- Rajamäki K, "Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3 inflammasome", J Biol Chem, 288, pp.13410~13419 (2013)
- Xu Z, "Distinct molecular mechanisms underlying potassium efflux for NLRP3 inflammasome activation", Front Immunol, 11, pp.609441~ (2020)
- Katsnelson MA, "K+ efflux agonists induce NLRP3 inflammasome activation independently of Ca2+ signaling", J Immunol, 194, pp.3937~3952 (2015)
- Muñoz-Planillo R, "K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter", Immunity, 38, pp.1142~1153 (2013)
- Tang T, "CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation", Nat Commun, 8, pp.202~ (2017)
- Daniels MJ, "Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models", Nat Commun, 7, pp.12504~ (2016)
- Green JP, "Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming", Proc Natl Acad Sci U S A, 115, pp.E9371~E9380 (2018)
- Verhoef PA, "Inhibitory effects of chloride on the activation of caspase-1, IL-1beta secretion, and cytolysis by the P2X7 receptor", J Immunol, 175, pp.7623~7634 (2005)
- Warton K, "Recombinant CLIC1(NCC27)assembles in lipid bilayers via a pH-dependent two-state process to form chloride ion channels with identical characteristics to those observed in Chinese hamster ovary cells expressing CLIC1", J Biol Chem, 277, pp.26003~26011 (2002)
- Domingo-Fernández R, "The intracellular chloride channel proteins CLIC1 and CLIC4 induce IL-1β transcription and activate the NLRP3 inflammasome", J Biol Chem, 292, pp.12077~12087 (2017)
- Kolaczkowska E, "Neutrophil recruitment and function in health and inflammation", Nat Rev Immunol, 13, pp.159~175 (2013)
- Filep JG, "Targeting neutrophils for promoting the resolution of inflammation", Front Immunol, 13, pp.866747~ (2022)
- Son S, "Neutrophils facilitate prolonged inflammasome response in the DAMP-rich inflammatory milieu", Front Immunol, 12, pp.746032~ (2021)
- Fernandes-Alnemri T, "AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA", Nature, 458, pp.509~513 (2009)
- McKenzie BA, "Fiery cell death : pyroptosis in the central nervous system", Trends Neurosci, 43, pp.55~73 (2020)
- Karmakar M, "Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP", Nat Commun, 7, pp.10555~ (2016)
- Lee GS, "The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP", Nature, 492, pp.123~127 (2012)
- Schorn C, "Sodium overload and water influx activate the NALP3 inflammasome", J Biol Chem, 286, pp.35~41 (2011)
- Mollinedo F, "Acidification activity of human neutrophils. Tertiary granules as a site of ATP-dependent acidification", J Biol Chem, 261, pp.1077~1082 (1986)
- Paroutis P, "The pH of the secretory pathway : measurement, determinants, and regulation", Physiology(Bethesda), 19, pp.207~215 (2004)