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,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,protein:increased expression:lung:RGD 
Il33Mousechronic obstructive pulmonary disease  IEP mRNA,protein:increased expression:lung:RGD 
IL1RL1Humanpulmonary emphysema treatmentISOIl1rl1 (Mus musculus)associated with common cold;RGD 
Il1rl1Ratpulmonary emphysema treatmentISOIl1rl1 (Mus musculus)associated with common cold;RGD 
Il1rl1Mousepulmonary emphysema treatmentIMP associated with common cold;RGD 

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