title: Low extracellular pH stimulates the production of IL-1β by human monocytes.
abstract: The development of acidic environments is a hallmark of inflammatory processes of different etiology. We have previously shown that transient exposure to acidic conditions, similar to those encountered in vivo, induces the activation of neutrophils and the phenotypic maturation of dendritic cells. We here report that extracellular acidosis (pH 6.5) selectively stimulates the production and the secretion of IL-1β by human monocytes without affecting the production of TNF-α, IL-6 and the expression of CD40, CD80, CD86, and HLA-DR. Stimulation of IL-1β production by pH 6.5-treated monocytes was shown to be dependent on caspase-1 activity, and it was also observed using peripheral blood mononuclear cells instead of isolated monocytes. Contrasting with the results in monocytes, we found that pH 6.5 did not stimulate any production of IL-1β by macrophages. Changes in intracellular pH seem to be involved in the stimulation of IL-1β production. In fact, monocytes cultured at pH 6.5 undergo a fall in the values of intracellular pH while the inhibitor of the Na+/H+ exchanger, 5-(N-ethyl-N-isopropyl)amiloride induced both, a decrease in the values of intracellular pH and the stimulation of IL-1β production. Real time quantitative PCR assays indicated that monocytes cultured either at pH 6.5 or in the presence of 5-(N-ethyl-N-isopropyl)amiloride expressed higher levels of pro-IL-1β mRNA suggesting that low values of intracellular pH enhance the production of IL-1β, at least in part, by stimulating the synthesis of its precursor.
authors.affiliation: Instituto de Investigaciones Hematológicas (IIHEMA), Academia Nacional de Medicina, Buenos Aires, Argentina. cjancic@hematologia.anm.edu.ar
authors.forename: Carolina Cristina
authors.initials: CC
authors.lastname: Jancic
authors.forename: Mercedes
authors.initials: M
authors.lastname: Cabrini
authors.forename: María Laura
authors.initials: ML
authors.lastname: Gabelloni
authors.forename: Christian
authors.initials: C
authors.lastname: Rodríguez Rodrigues
authors.forename: Gabriela
authors.initials: G
authors.lastname: Salamone
authors.forename: Analía Silvina
authors.initials: AS
authors.lastname: Trevani
authors.forename: Jorge
authors.initials: J
authors.lastname: Geffner
mesh_terms: D002118:Calcium / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D002470:Cell Survival; D003600:Cytosol / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010641:Phenotype
chemical_list: D053583:Interleukin-1beta; D020170:Caspase 1; D002118:Calcium