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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Respiratory Research 1/2018

IL-1β mediates lung neutrophilia and IL-33 expression in a mouse model of viral-induced asthma exacerbation

Zeitschrift:
Respiratory Research > Ausgabe 1/2018
Autoren:
Irma Mahmutovic Persson, Mandy Menzel, Sangeetha Ramu, Samuel Cerps, Hamid Akbarshahi, Lena Uller
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12931-018-0725-z) contains supplementary material, which is available to authorized users.

Abstract

Background

Viral-induced asthma exacerbations, which exhibit both Th1-type neutrophilia and Th2-type inflammation, associate with secretion of Interleukin (IL)-1β. IL-1β induces neutrophilic inflammation. It may also increase Th2-type cytokine expression. We hypothesised that IL-1β is causally involved in both Th1 and Th2 features of asthma exacerbations. This hypothesis is tested in our mouse model of viral stimulus-induced asthma exacerbation.

Method

Wild-type (WT) and IL-1β deficient (IL-1β−/−) mice received house dust mite (HDM) or saline intranasally during three weeks followed by intranasal dsRNA (PolyI:C molecule known for its rhinovirus infection mimic) for three consecutive days to provoke exacerbation. Bronchoalveolar lavage fluid was analysed for inflammatory cells and total protein. Lung tissues were stained for neutrophilic inflammation and IL-33. Tissue homogenates were analysed for mRNA expression of Muc5ac, CXCL1/KC, TNF-α, CCL5, IL-25, TSLP, IL-33, IL-1β, CCL11 and CCL2 using RT-qPCR.

Results

Expression of IL-1β, neutrophil chemoattractants, CXCL1 and CCL5, the Th2-upstream cytokine IL-33, and Muc5ac were induced at exacerbation in WT mice and were significantly inhibited in IL-1β−/− mice at exacerbation. Effects of HDM alone were not reduced in IL-1β-deficient mice.

Conclusion

Without being involved in the baseline HDM-induced allergic asthma, IL-1β signalling was required to induce neutrophil chemotactic factors, IL-33, and Muc5ac expression at viral stimulus-induced exacerbation. We suggest that IL-1β has a role both in neutrophilic and Th2 inflammation at viral-induced asthma exacerbations.
Zusatzmaterial
Additional file 1: Figure S1. IL-1β mRNA expression induced at exacerbation in the WT mice while completely abolished in both IL-1β−/− groups. mRNA was measured from lung tissue homogenates by RT-qPCR. The relative gene expression was related to the reference gene 18S and normalised to control. Data are presented as mean ± SEM, n = 4–7 mice in each group. ## = p < 0.01 compared to respective HDM/Saline control and comparison between WT and IL-1β−/−, at exacerbation is indicated by ** = p < 0.01. (TIFF 542 kb)
12931_2018_725_MOESM1_ESM.tif
Additional file 2: Table S1. Commercially available primer sequences for genes analysed with RT-qPCR. (DOCX 13 kb)
12931_2018_725_MOESM2_ESM.docx
Additional file 3: Figure S2. Increased immune cells and total protein in BALF in both WT and IL-1β−/− groups 24 h after the last HDM challenge alone. Total protein in BALF (a), total cells from BALF (b) and total neutrophil count in BALF (c). Data are presented as mean ± SEM, n = 4–7 mice in each group. ## = p < 0.01 compared to respective HDM/Saline control, and # = p < 0.05 compared to respective HDM/Saline control. (TIFF 941 kb)
12931_2018_725_MOESM3_ESM.tif
Additional file 4: Figure S3. Increased immune cell count and chemokine expression at exacerbation, although in both WT and IL-1β−/− mice. Total eosinophil count (a), macrophage count (b) and lymphocyte count (c) from BALF at exacerbation. Chemokine mRNA expression of CCL11 (d) and CCL2 (e) from lung tissue homogenates were analysed with RT-qPCR. The relative gene expression was related to the reference gene 18S and normalised to control. Data are presented as mean ± SEM, n = 4–8 mice in each group. ## = p < 0.01 compared to respective HDM/Saline control. (TIFF 1200 kb)
12931_2018_725_MOESM4_ESM.tif
Literatur
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