RGD Reference Report - Rhinovirus-induces progression of lung disease in a mouse model of COPD via IL-33/ST2 signaling axis. - Rat Genome Database

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Rhinovirus-induces progression of lung disease in a mouse model of COPD via IL-33/ST2 signaling axis.

Authors: Gimenes, Joao A  Srivastava, Vikram  ReddyVari, Hymavathi  Kotnala, Sudhir  Mishra, Rahul  Farazuddin, Mohamed  Li, Wuyan  Sajjan, Umadevi S 
Citation: Gimenes JA, etal., Clin Sci (Lond). 2019 Apr 29;133(8):983-996. doi: 10.1042/CS20181088. Print 2019 Apr 30.
RGD ID: 40400740
Pubmed: PMID:30952808   (View Abstract at PubMed)
PMCID: PMC9585538   (View Article at PubMed Central)
DOI: DOI:10.1042/CS20181088   (Journal Full-text)

Rhinovirus (RV), which is associated with acute exacerbations, also causes persistent lung inflammation in patients with chronic obstructive pulmonary disease (COPD), but the underlying mechanisms are not well-known. Recently, we demonstrated that RV causes persistent lung inflammation with accumulation of a subset of macrophages (CD11b+/CD11c+), and CD8+ T cells, and progression of emphysema. In the present study, we examined the mechanisms underlying the RV-induced persistent inflammation and progression of emphysema in mice with COPD phenotype. Our results demonstrate that at 14 days post-RV infection, in addition to sustained increase in CCL3, CXCL-10 and IFN-γ expression as previously observed, levels of interleukin-33 (IL-33), a ligand for ST2 receptor, and matrix metalloproteinase (MMP)12 are also elevated in mice with COPD phenotype, but not in normal mice. Further, MMP12 was primarily expressed in CD11b+/CD11c+ macrophages. Neutralization of ST2, reduced the expression of CXCL-10 and IFN-γ and attenuated accumulation of CD11b+/CD11c+ macrophages, neutrophils and CD8+ T cells in COPD mice. Neutralization of IFN-γ, or ST2 attenuated MMP12 expression and prevented progression of emphysema in these mice. Taken together, our results indicate that RV may stimulate expression of CXCL-10 and IFN-γ via activation of ST2/IL-33 signaling axis, which in turn promote accumulation of CD11b+/CD11c+ macrophages and CD8+ T cells. Furthermore, RV-induced IFN-γ stimulates MMP12 expression particularly in CD11b+/CD11c+ macrophages, which may degrade alveolar walls thus leading to progression of emphysema in these mice. In conclusion, our data suggest an important role for ST2/IL-33 signaling axis in RV-induced pathological changes in COPD mice.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL1RL1Humanchronic obstructive pulmonary disease  ISOIl1rl1 (Mus musculus)mRNA:increased expression:lung:RGD 
IL33Humanchronic obstructive pulmonary disease  ISOIl33 (Mus musculus)mRNA and protein:increased expression:lung:RGD 
Il1rl1Ratchronic obstructive pulmonary disease  ISOIl1rl1 (Mus musculus)mRNA:increased expression:lung:RGD 
Il1rl1Mousechronic obstructive pulmonary disease  IEP mRNA:increased expression:lung:RGD 
Il33Ratchronic obstructive pulmonary disease  ISOIl33 (Mus musculus)mRNA and protein:increased expression:lung:RGD 
Il33Mousechronic obstructive pulmonary disease  IEP mRNA and protein:increased expression:lung:RGD 
IL1RL1Humanpulmonary emphysema treatmentISOIl1rl1 (Mus musculus)associated with common coldRGD 
Il1rl1Ratpulmonary emphysema treatmentISOIl1rl1 (Mus musculus)associated with common coldRGD 
Il1rl1Mousepulmonary emphysema treatmentIMP associated with common coldRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1rl1  (interleukin 1 receptor-like 1)
Il33  (interleukin 33)

Genes (Mus musculus)
Il1rl1  (interleukin 1 receptor-like 1)
Il33  (interleukin 33)

Genes (Homo sapiens)
IL1RL1  (interleukin 1 receptor like 1)
IL33  (interleukin 33)


Additional Information