8 research outputs found
Effect of ISO-1 and dexamethasone on ozone-induced changes in AHR and lung function.
<p>Mouse lung function measurements of pulmonary resistance (R<sub>L</sub>; A), -logPC<sub>100</sub> (B), FEV<sub>75</sub> (C), lung compliance (C<sub>chord</sub>; D), total lung capacity (TLC; E) and functional residual capacity (FRC; F). Data are expressed as mean±SD for 6 animals per group. *<i>p</i><0.05 and **<i>p</i><0.01 compared to air controls, <sup>#</sup><i>p</i><0.05 compared to ozone-exposed group.</p
Effect of ISO-1 and dexamethasone on ozone-induced BAL inflammation.
<p>Cytokine protein levels in mouse BAL of ozone exposed and ISO-1- or dexamethasone-treated mice measured by ELISA. KC (A), GM-CSF (B), TNF-α (C) and MIF (D). Data are expressed as mean±SD for 6 animals per group. *<i>p</i><0.05 and **<i>p</i><0.01 compared to air controls, # <i>p</i><0.05 compared to ozone exposed group.</p
Effect of ISO-1 and dexamethasone on ozone-induced lung inflammation.
<p>Cytokine mRNA (A, C, E & G) and protein (B, D, F & H) expression levels in the lung of ozone exposed and ISO-1- or dexamethasone-treated mice. KC (A&B), GM-CSF (C&D), TNF-α (E&F), and MIF (G&H). Data are expressed as mean±SD for 6 animals per group. *<i>p</i><0.05 and **<i>p</i><0.01 compared to air controls, <sup>#</sup><i>p</i><0.05 compared to ozone exposed group.</p
Effect of ISO-1 and dexamethasone in combination on ozone-induced lung inflammation.
<p>Cytokine mRNA (A & C) and protein (B & D) expression levels in the lung of ozone exposed and the combination of ISO-1- plus dexamethasone-treated mice. KC (A&B) and MIF (C&D). Pulmonary resistance (R<sub>L;</sub> E) was also measured. Data are expressed as mean±SD for 6 animals per group. *<i>p</i><0.05 and **<i>p</i><0.01 compared to air controls, <sup>#</sup><i>p</i><0.05 compared to ozone exposed group.</p
Change in soluble fractalkine in BAL fluid during experimental <i>in vivo</i> RV16 infection, related with upper respiratory symptom scores.
<p>Soluble fractalkine protein was measured in filtered BAL fluid collected at baseline and day 4 post RV16 infection from non-asthmatic (n = 10), mild-asthmatic (n = 11) and moderate-asthmatic (n = 14) subjects. (A) Data is presented as soluble fractalkine (pg/mL) per subject and horizontal bars for median levels for each group in BAL fluid obtained at baseline and day 4. Data were analysed within groups by Wilcoxon-matched pairs signed rank tests and between groups by Mann Whitney U test, *P<0.05. (B) Levels of fractalkine in BAL fluid on Day 4 were correlated with peak upper respiratory symptom scores for each subject infected using Pearson’s correlation (r = 0.289, <i>P</i> = 0.098).</p
Change in levels of fractalkine in PBMCs following <i>in vitro</i> infection with RV16 and RV1B.
<p>Soluble fractalkine protein was measured in cell supernatants from PBMCs obtained from (A) non-asthmatic (n = 15) and (B) asthmatic (n = 15) subjects and compared between subject groups at 8hrs post infection (C). Fractalkine mRNA expression was measured in PBMC cell lysate cDNA obtained from (D) non-asthmatic and (E) asthmatic subjects. The results are expressed as mean ± SEM. Protein data were analysed by one-way ANOVA with Bonferroni post-test and mRNA by Kruskal Wallis with Dunn’s post test (*<i>P</i><0.05, ***<i>P</i><0.001).</p
Change in levels of fractalkine in BAL cells following <i>in vitro</i> infection with RV16 and RV1B.
<p>Soluble fractalkine protein was measured in cell supernatants from BAL cells obtained from (A) non-asthmatic (n = 15) and (B) asthmatic (n = 15) subjects and compared between subject groups at 8hrs post infection (C). Fractalkine mRNA expression was measured in BAL cell lysate cDNA obtained from non-asthmatic (D) and asthmatic (E) subjects. The results are expressed as mean ± SEM. Protein data were analysed by one-way ANOVA with Bonferroni post-test and mRNA by Kruskal Wallis with Dunn’s post test (**<i>P</i><0.01).</p
IL-33-dependent type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo
Rationale:
Rhinoviruses are the major cause of asthma
exacerbations; however, its underlying mechanisms are poorly
understood. We hypothesized that the epithelial cell–derived
cytokine IL-33 plays a central role in exacerbation pathogenesis
through augmentation of type 2 inflammation.
Objectives:
To assess whether rhinovirus induces a type 2
inflammatory response in asthma
in vivo
and to define a role for IL-33
in this pathway.
Methods:
We used a human experimental model of rhinovirus
infection and novel airway sampling techniques to measure IL-4, IL-5,
IL-13, and IL-33 levels in the asthmatic and healthy airways during
a rhinovirus infection. Additionally, we cultured human T cells and type
2 innate lymphoid cells (ILC2s) with the supernatants of rhinovirus-
infected bronchial epithelial cells (BECs) to assess type 2 cytokine
production in the presence or absence of IL-33 receptor blockade.
Measurements and Main Results:
IL-4, IL-5, IL-13, and IL-33 are
all induced by rhinovirus in the asthmatic airway in vivo and relate to
exacerbation severity. Further, induction of IL-33 correlates with
viral load and IL-5 and IL-13 levels. Rhinovirus infection of human
primary BECs induced IL-33, and culture of human T cells and ILC2s
with supernatants of rhinovirus-infected BECs strongly induced
type 2 cytokines. This induction was entirely dependent on IL-33.
Conclusions:
IL-33 and type 2 cytokines are induced during
a rhinovirus-induced asthma exacerbation in vivo. Virus-induced
IL-33 and IL-33
–
responsive T cells and ILC2s are key mechanistic
links between viral infection and exacerbation of asthma. IL-33
inhibition is a novel therapeutic approach for asthma exacerbations