Epithelial CXCL10 protein secreted into the basolateral compartment increases with increasing T cells numbers and increasing IFNγ and TNF amounts, reaching a plateau at high concentrations.

<p>A constant number of HNEC (0.5×10⁶ cells) was co-cultured with increasing numbers of activated T cells (0.1, 0.5, 2.5, 5×10⁶ cells). CXCL10 protein amounts secreted by HNEC into the basolateral media are expressed as a function of the numbers of T cells in co-cultures (A) and the amounts of IFNγ (B) and TNF (C) secreted by increasing numbers of T cells.</p

Activated T cells inhibit virus replication in infected HNEC partially through the NO pathway.

<p>HNEC were exposed apically to HRV14, washed thoroughly then co-cultured with activated T cells in the presence or absence of FP and L-NIL, inhibitors of NOS2 mRNA and activity, respectively. (A) NO secretion in the basolateral compartment and (B) viral RNA levels. NO is expressed as nitrite, the stable oxidation product of NO (µM). Viral RNAs was measured by real-time PCR and expressed as fold change relative to those observed in infected HNEC cultured in the absence of activated T cells. *p<0.05</p

Epithelial CXCL10 mRNA is induced by HRV14 and T cells, CXCL8 and IL-6 mRNA are induced only by T cells.

<p>HNEC were exposed apically to HRV14 alone (HRV), or co-cultured with activated T cells alone (T cells), or exposed to HRV14 washed thoroughly then co-cultured with activated T cells (HRV+T cells). The expression of CXCL10 mRNA (A), CXCL8 mRNA (B) and IL-6 mRNA (C) was determined by real-time PCR. Data represent the fold increase relative to non-infected cells cultured in the absence of T cells. Shown are the boxplots with the 25^th, 50^th (median), 75^th percentiles, the mean (open square), the maximum and the minimum values. *p<0.05 compared with control non-infected cells. **p<0.05 compared with HRV-infected cells.</p

Epithelial NOS2 mRNA expression and NO release are induced by T cells but not HRV14.

<p>HNEC were either not infected (C) or exposed apically to HRV14 alone (HRV), or co-cultured with activated T cells alone (T cells), or exposed to HRV14 washed thoroughly then co-cultured with activated T cells (HRV+T cells). (A) mRNA was determined by real-time PCR and data represented as fold increase relative to non-infected cells cultured without T cells. (B) NO secretion is expressed as the amount of nitrite (the stable oxidation product of NO) released in the apical and basolateral compartments (µM). Shown are the boxplots with the 25^th, 50^th (median), 75^th percentiles, the mean (open square), the maximum and the minimum values. *p<0.05. **p<0.05 compared with HRV-infected cells.</p

Anti-IFNγ and TNF soluble receptor p75 strongly reduce epithelial CXCL10 mRNA expression but only partially attenuate epithelial NOS2 expression induced by T cells.

<p>HNEC were co-cultured with activated T cells in the absence or presence of anti-IFNγ, TNF soluble receptor (srTNF) or an isotype-matched antibody (IgG). CXCL10 (A) and NOS2 (B) mRNA were measured by real-time PCR. Data are presented as fold change relative to those obtained in the absence of neutralizing agents. Shown are the boxplots with the 25^th, 50^th (median), 75^th percentiles, the mean (open square), the maximum and the minimum values. *p<0.05 compared with isotype matched IgG treated cultures. #p<0.05 compared with anti-IFNγ and srTNF treated cultures.</p

Effect modification by vigorous physical activity.

<p>MetS-W: Metabolic syndrome according to World Health Organization. MetS-I: Metabolic syndrome according to International Diabetes Federation. MetS-A: Metabolic syndrome according to Adult Treatment Panel-III criteria. Active defined as vigorous physical activity ≥30 minutes per week. Inactive defined as vigorous physical activity <30minutes per week. Fully adjusted models include age, sex, educational attainment, neighbourhood socio-economic index, occupational exposure to vapours, gases, dusts and fumes, smoking status, smoked pack-years, exposure to passive smoke, consumption of fruits and raw vegetables, and body mass index. PM₁₀: particulate matter <10μm in diameter from all sources. All analyses were done with four-hour fasting participants. Participants’ study area was treated as a random effect in all models. Odds ratio values refer to increments of 10μg/m³ in PM₁₀ exposure. Total N = 3684; N(physically-active) = 2115.</p

Sensitivity Analyses.

<p>Fully adjusted models include age, sex, educational attainment, neighbourhood socio-economic index, occupational exposure to vapours, gases, dusts and fumes, smoking status, smoked pack-years, exposure to passive smoke, consumption of fruits and raw vegetables, physical activity and body mass index. MI: multiple imputations. IPW: inverse probability weighting. PM₁₀: particulate matter <10μm in diameter from all sources. NO₂: nitrogen dioxide. OR: odds ratio. CI: confidence interval. OR refer to increments of 10μg/m³ in PM₁₀, and NO₂ exposure respectively. All analyses were done with four-hour fasting participants.</p><p>Sensitivity Analyses.</p

Effect modification by smoking status.

<p>MetS-W: Metabolic syndrome according to World Health Organization. MetS-I: Metabolic syndrome according to International Diabetes Federation. MetS-A: Metabolic syndrome according to Adult Treatment Panel-III criteria. Fully adjusted models include age, sex, educational attainment, neighbourhood socio-economic index, occupational exposure to vapours, gases, dusts and fumes, exposure to passive smoke, consumption of fruits and raw vegetables, physical activity and body mass index. PM₁₀: particulate matter <10μm in diameter from all sources. All analyses were done with four-hour fasting participants. Participants’ study area was treated as a random effect in all models. Odds ratio values refer to increments of 10μg/m³ in PM₁₀ exposure. Total N = 3684; N(never-smoker) = 1623.</p

Effect modification by sex.

<p>MetS-W: Metabolic syndrome according to World Health Organization. MetS-I: Metabolic syndrome according to International Diabetes Federation. MetS-A: Metabolic syndrome according to Adult Treatment Panel-III criteria. Fully adjusted models include age, educational attainment, neighbourhood socio-economic index, occupational exposure to vapours, gases, dusts and fumes, smoking status, smoked pack-years, exposure to passive smoke, consumption of fruits and raw vegetables, physical activity and body mass index. PM₁₀: particulate matter <10μm in diameter from all sources. NO₂: nitrogen dioxide. All analyses were done with four-hour fasting participants. Participants’ study area was treated as a random effect in all models. Odds ratio values refer to increments of 10μg/m³ in PM₁₀ exposure. Total N = 3684; N(males) = 1746.</p

Effect modification by age group.

<p>MetS-W: Metabolic syndrome according to World Health Organization. MetS-I: Metabolic syndrome according to International Diabetes Federation. MetS-A: Metabolic syndrome according to Adult Treatment Panel-III criteria. Fully adjusted models include sex, educational attainment, neighbourhood socio-economic index, occupational exposure to vapours, gases, dusts and fumes, smoking status, smoked pack-years, exposure to passive smoke, consumption of fruits and raw vegetables, physical activity and body mass index. PM₁₀: particulate matter <10μm in diameter from all sources. All analyses were done with four-hour fasting participants. Participants’ study area was treated as a random effect in all models. Odds ratio values refer to increments of 10μg/m³ in PM₁₀ exposure. Total N = 3684; N(age≤50) = 1393.</p