title: Vanadium pentoxide prevents NK-92MI cell proliferation and IFNγ secretion through sustained JAK3 phosphorylation.
abstract: Vanadium is a major air pollutant with toxic and carcinogenic effects; it also exercises immunosuppressive effects on the adaptive immune response. Its effect on the innate immune response is poorly explored. The aim of this study was to identify if vanadium pentoxide (V2O5) impairs the function of immunoregulatory NK cells and to determine possible mechanisms associated with this effect. Interleukin-2-independent NK-92MI cells were exposed to different V2O5 concentrations for 6, 12, or 24 h periods. Cell proliferation was then evaluated using CFSE staining, apoptosis by Annexin V binding, and necrosis by 7-AAD staining. The release of IL-2, -4, -6, -10, -17A, IFNγ, and TNFα by the cells were assessed using a human CBA kit. Expression of CD45, SOCS1, JAK3, pJAK3, STAT5, pSTAT5, IL-2R, IL-15R, Fas, and FasL in/on the cells was determined by flow cytometry; JAK3 and pJAK3 expression were also evaluated via confocal microscopy. The results indicated that V2O5 could inhibit NK-92MI cell proliferation and induce cell apoptosis in a dose- and time-related manner. V2O5 also inhibited IL-2, IL-10, and IFNγ secretion but mostly only after 24 h of exposure and with primarily the higher doses tested. V2O5 had no effect on expression of JAK3 and STAT5, but did cause an increase in pJAK3 and appeared to lead (trend) to reductions in levels of phosphorylated STAT5. V2O5 increased the expression of IL-2R, IL-15R, Fas, and FasL at concentrations above the 50-100 µM range. V2O5 had no effect on expression of the CD45 membrane phosphatase, but it did cause an increase in the expression of SOCS1. These results indicate that a key toxic effect of V2O5 on NK cells is a dysregulation of signaling pathways mediated by IL-2. These effects could help to explain the previously-reported deleterious effects on innate immune responses of hosts exposed to inhaled V2O5.
authors.affiliation: a Laboratorio Inmunobiología, Departamento de Biología Celular y Tisular, Facultad de Medicina .
authors.forename: Francisco
authors.initials: F
authors.lastname: Gallardo-Vera
authors.affiliation: b Departamento de Biología Celular y Fisiología .
authors.forename: Daniel
authors.initials: D
authors.lastname: Diaz
authors.affiliation: c Unidad de Microscopia , Instituto de Investigaciones Biomédicas, UNAM , México , and.
authors.forename: Miguel
authors.initials: M
authors.lastname: Tapia-Rodriguez
authors.affiliation: a Laboratorio Inmunobiología, Departamento de Biología Celular y Tisular, Facultad de Medicina .
authors.forename: Teresa
authors.initials: T
authors.lastname: Fortoul van der Goes
authors.affiliation: d Departamento de Fisiología , Instituto Nacional de Cardiología 'Ignacio Chávez' , México.
authors.forename: Felipe
authors.initials: F
authors.lastname: Masso
authors.affiliation: a Laboratorio Inmunobiología, Departamento de Biología Celular y Tisular, Facultad de Medicina .
authors.forename: Erika
authors.initials: E
authors.lastname: Rendon-Huerta
authors.affiliation: a Laboratorio Inmunobiología, Departamento de Biología Celular y Tisular, Facultad de Medicina .
authors.forename: Luis F
authors.initials: LF
authors.lastname: Montaño
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D053616:Janus Kinase 3 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D017968:Vanadium Compounds / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D002273:Carcinogens; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D017968:Vanadium Compounds; D007371:Interferon-gamma; C066075:vanadium pentoxide; D053616:Janus Kinase 3
keywords: Cytokines; Fas-FasL; JAK/STAT; NK cells; SOCS; vanadium pentoxide