Effects of environmental air pollutants on CFTR expression and function in human airway epithelial cells.

Homo sapiens diesel exhaustrespirable suspended particulate mattersmoke

Study subjects

soma:nguyen-calu3-001

Calu-3 human airway epithelial cells

type: CellularSystem Homo sapiens NCBITaxon:9606 epithelial cell CL:0000066

CFTR assays

CFTR:nguyen-tse-24h

CFTR function - Calu-3, tobacco smoke extract 24 h

CFTR function in Calu-3 human airway epithelial cells after 24 h exposure to tobacco smoke extract. The abstract reports that tobacco smoke extract led to acquired CFTR dysfunction. No magnitude, concentration, sample size or p-value is reported in the abstract, so the output records carry no values.

Exposure conditions

ConditionAgentConcentrationDuration
Vehicle control, 24 hours (unexposed Calu-3)
EXPOSURE:nguyen-vehicle-24h
— — 24 hour
Tobacco smoke extract for 24 hours (concentration not reported in abstract)
EXPOSURE:nguyen-tse-24h
smoke
ENVO:01000838
— 24 hour

Outputs

GroupOutputDescription
vehicle_control Vehicle control CFTR function (no values reported in abstract)
CFTR:nguyen-tse-24h-output-control · under EXPOSURE:nguyen-vehicle-24h
treated Tobacco smoke extract CFTR function - dysfunction reported, no values in abstract
CFTR:nguyen-tse-24h-output-tse · under EXPOSURE:nguyen-tse-24h

Evidence

We demonstrate that both tobacco smoke extract and diesel exhaust particles led to acquired CFTR dysfunction
SUPPORT IN VITRO PMID:34601066

The abstract's stated result names tobacco smoke extract as one of the two pollutants that produced acquired CFTR dysfunction, which is the decreased CFTR function this assay's treated output records.

CFTR:nguyen-upm-24h

CFTR function - Calu-3, urban particulate matter 24 h

CFTR function in Calu-3 cells after 24 h exposure to urban particulate matter. Urban particulate matter was one of the three pollutants the study set out to test, but the abstract's result sentence names only tobacco smoke extract and diesel exhaust particles as causing acquired CFTR dysfunction. Recorded here as a tested exposure with REFUTE evidence against decreased CFTR function; the abstract reports no values.

Exposure conditions

ConditionAgentConcentrationDuration
Vehicle control, 24 hours (unexposed Calu-3)
EXPOSURE:nguyen-vehicle-24h
— — 24 hour
Urban particulate matter for 24 hours (concentration not reported in abstract)
EXPOSURE:nguyen-upm-24h
respirable suspended particulate matter
ENVO:01000405
— 24 hour

Outputs

GroupOutputDescription
vehicle_control Vehicle control CFTR function (no values reported in abstract)
CFTR:nguyen-upm-24h-output-control · under EXPOSURE:nguyen-vehicle-24h
treated Urban particulate matter CFTR function - no dysfunction reported, no values in abstract
CFTR:nguyen-upm-24h-output-upm · under EXPOSURE:nguyen-upm-24h

Evidence

The aim of our study was to test whether environmental air pollutants tobacco smoke extract, urban particulate matter, and diesel exhaust particles lead to acquired CFTR dysfunction
SUPPORT IN VITRO PMID:34601066

The abstract's aim sentence establishes that urban particulate matter was one of the three pollutant exposures actually tested against CFTR readouts, which is what this assay record's exposure condition represents.

We demonstrate that both tobacco smoke extract and diesel exhaust particles led to acquired CFTR dysfunction
REFUTE IN VITRO PMID:34601066

The result sentence attributes acquired CFTR dysfunction to tobacco smoke extract and diesel exhaust particles only, so it argues against decreased CFTR function for the urban particulate matter arm.

CFTR:nguyen-dep-24h

CFTR function - Calu-3, diesel exhaust particles 24 h

CFTR function in Calu-3 cells after 24 h exposure to diesel exhaust particles. The abstract reports that diesel exhaust particles led to acquired CFTR dysfunction. No magnitude, concentration, sample size or p-value is reported in the abstract.

Exposure conditions

ConditionAgentConcentrationDuration
Vehicle control, 24 hours (unexposed Calu-3)
EXPOSURE:nguyen-vehicle-24h
— — 24 hour
Diesel exhaust particles for 24 hours (concentration not reported in abstract)
EXPOSURE:nguyen-dep-24h
diesel exhaust
ENVO:03510008
— 24 hour

Outputs

GroupOutputDescription
vehicle_control Vehicle control CFTR function (no values reported in abstract)
CFTR:nguyen-dep-24h-output-control · under EXPOSURE:nguyen-vehicle-24h
treated Diesel exhaust particle CFTR function - dysfunction reported, no values in abstract
CFTR:nguyen-dep-24h-output-dep · under EXPOSURE:nguyen-dep-24h

Evidence

We demonstrate that both tobacco smoke extract and diesel exhaust particles led to acquired CFTR dysfunction and that rescue of acquired CFTR dysfunction is possible with pharmacological interventions in diesel exhaust particle models.
SUPPORT IN VITRO PMID:34601066

The abstract's result sentence names diesel exhaust particles as a pollutant that produced acquired CFTR dysfunction, which is the decreased CFTR function this assay's treated output records.

CFTR:nguyen-dep-rescue-24h

CFTR function rescue - Calu-3, diesel exhaust particles plus pharmacological intervention, 24 h

CFTR function in Calu-3 cells co-treated with diesel exhaust particles and a pharmacological intervention for 24 h. The abstract reports that rescue of acquired CFTR dysfunction was possible with pharmacological interventions in the diesel exhaust particle models, but does not name the drug(s), the concentration, or the size of the rescue, so no agent term or value is asserted for the intervention.

Exposure conditions

ConditionAgentConcentrationDuration
Diesel exhaust particles for 24 hours (concentration not reported in abstract)
EXPOSURE:nguyen-dep-24h
diesel exhaust
ENVO:03510008
— 24 hour
Diesel exhaust particles plus pharmacological intervention for 24 hours (intervention not named in abstract)
EXPOSURE:nguyen-dep-plus-drug-24h
diesel exhaust
ENVO:03510008
— 24 hour

Outputs

GroupOutputDescription
treated Diesel exhaust particles alone, CFTR function (no values reported in abstract)
CFTR:nguyen-dep-rescue-24h-output-dep · under EXPOSURE:nguyen-dep-24h
treated Diesel exhaust particles plus pharmacological intervention, CFTR function rescued (no values in abstract)
CFTR:nguyen-dep-rescue-24h-output-dep-drug · under EXPOSURE:nguyen-dep-plus-drug-24h

Evidence

rescue of acquired CFTR dysfunction is possible with pharmacological interventions in diesel exhaust particle models
SUPPORT IN VITRO PMID:34601066

The abstract states directly that pharmacological intervention restored CFTR function in the diesel exhaust particle exposure, which is what this rescue arm records.

Gene expression assays

GE:nguyen-cftr-expression-tse-24h

CFTR expression - Calu-3, tobacco smoke extract 24 h

CFTR protein expression readout in Calu-3 cells after 24 h tobacco smoke extract exposure. The abstract states CFTR expression was measured but does not report the result, so the output record carries no value.

target gene: PR:000003411 gene expression method: Western blot

Exposure conditions

ConditionAgentConcentrationDuration
Vehicle control, 24 hours (unexposed Calu-3)
EXPOSURE:nguyen-vehicle-24h
— — 24 hour
Tobacco smoke extract for 24 hours (concentration not reported in abstract)
EXPOSURE:nguyen-tse-24h
smoke
ENVO:01000838
— 24 hour

Outputs

GroupOutputDescription
vehicle_control Vehicle control CFTR expression (no values reported in abstract)
GE:nguyen-cftr-expression-tse-24h-output-control · under EXPOSURE:nguyen-vehicle-24h
treated Tobacco smoke extract CFTR expression (no values reported in abstract)
GE:nguyen-cftr-expression-tse-24h-output-tse · under EXPOSURE:nguyen-tse-24h

Evidence

Human airway epithelial cells (Calu-3) were exposed to air pollutant extracts for 24 h, with and without pharmacological interventions, with readouts of CFTR expression and function.
SUPPORT IN VITRO PMID:34601066

The methods sentence of the abstract establishes that CFTR expression was read out in Calu-3 cells after a 24 h air pollutant extract exposure, which is exactly what this assay record captures; the abstract reports no expression value, so none is recorded.

GE:nguyen-cftr-expression-upm-24h

CFTR expression - Calu-3, urban particulate matter 24 h

CFTR protein expression readout in Calu-3 cells after 24 h urban particulate matter exposure. The abstract states CFTR expression was measured but does not report the result, so the output record carries no value.

target gene: PR:000003411 gene expression method: Western blot

Exposure conditions

ConditionAgentConcentrationDuration
Vehicle control, 24 hours (unexposed Calu-3)
EXPOSURE:nguyen-vehicle-24h
— — 24 hour
Urban particulate matter for 24 hours (concentration not reported in abstract)
EXPOSURE:nguyen-upm-24h
respirable suspended particulate matter
ENVO:01000405
— 24 hour

Outputs

GroupOutputDescription
vehicle_control Vehicle control CFTR expression (no values reported in abstract)
GE:nguyen-cftr-expression-upm-24h-output-control · under EXPOSURE:nguyen-vehicle-24h
treated Urban particulate matter CFTR expression (no values reported in abstract)
GE:nguyen-cftr-expression-upm-24h-output-upm · under EXPOSURE:nguyen-upm-24h

Evidence

with readouts of CFTR expression and function
SUPPORT IN VITRO PMID:34601066

The abstract names CFTR expression as one of the two readouts taken on the pollutant-exposed Calu-3 cells, which is what this urban particulate matter expression record documents; no expression value is reported, so none is recorded.

GE:nguyen-cftr-expression-dep-24h

CFTR expression - Calu-3, diesel exhaust particles 24 h

CFTR protein expression readout in Calu-3 cells after 24 h diesel exhaust particle exposure. The abstract states CFTR expression was measured but does not report the result, so the output record carries no value.

target gene: PR:000003411 gene expression method: Western blot

Exposure conditions

ConditionAgentConcentrationDuration
Vehicle control, 24 hours (unexposed Calu-3)
EXPOSURE:nguyen-vehicle-24h
— — 24 hour
Diesel exhaust particles for 24 hours (concentration not reported in abstract)
EXPOSURE:nguyen-dep-24h
diesel exhaust
ENVO:03510008
— 24 hour

Outputs

GroupOutputDescription
vehicle_control Vehicle control CFTR expression (no values reported in abstract)
GE:nguyen-cftr-expression-dep-24h-output-control · under EXPOSURE:nguyen-vehicle-24h
treated Diesel exhaust particle CFTR expression (no values reported in abstract)
GE:nguyen-cftr-expression-dep-24h-output-dep · under EXPOSURE:nguyen-dep-24h

Evidence

exposed to air pollutant extracts for 24 h, with and without pharmacological interventions, with readouts of CFTR expression and function
SUPPORT IN VITRO PMID:34601066

This fragment of the abstract's methods sentence establishes the 24 h pollutant-extract exposure and the CFTR expression readout that this diesel exhaust particle record captures; the abstract reports no expression value.

Key-event relationships

KER:nguyen-cftr-to-mcc

Decreased CFTR function leads to impaired mucociliary clearance

Framing stated in the abstract's background: mucociliary clearance defends the airway against environmental air pollutants and is regulated by ion transporters including CFTR, so pollutant-acquired CFTR dysfunction acts on mucociliary clearance. Asserted as background in this paper, not measured in it.

Mucociliary clearance is an important host defense mechanism against environmental air pollutants and this process is regulated by various ion transporters including the cystic fibrosis transmembrane conductance regulator (CFTR).
SUPPORT IN VITRO PMID:34601066

The abstract states that mucociliary clearance is regulated by CFTR, which is the causal link from decreased CFTR function to impaired mucociliary clearance recorded here; the paper states it as background rather than measuring clearance, hence weak support.

Protocols

PROTOCOL:nguyen-exposure-001

Calu-3 air pollutant extract exposure, 24 hours

Human airway epithelial cells (Calu-3) exposed to air pollutant extracts (tobacco smoke extract, urban particulate matter, or diesel exhaust particles) for 24 h, with and without pharmacological interventions. Extract preparation, concentrations and vehicle are not reported in the abstract, which is the only text available for this paper.

PROTOCOL:nguyen-cftr-function-001

CFTR function readout in Calu-3 cells

Electrophysiological readout of CFTR function after 24 h pollutant extract exposure. The abstract states only that CFTR function was a readout; the cached record is indexed under the MeSH heading 'Membrane Potentials/drug effects'. Chamber type, stimulation agent, inhibitor and units are not reported in the abstract.

PROTOCOL:nguyen-cftr-expression-001

CFTR expression readout by immunoblot

CFTR protein expression measured after 24 h pollutant extract exposure. The abstract states only that CFTR expression was a readout; the cached record is indexed under the MeSH heading 'Blotting, Western'. Antibodies, loading control and quantification are not reported in the abstract.