The role of the CCR1 receptor in the inflammatory response to tobacco smoke in a mouse model

Önnervik, Per Ola; Lindahl, Maria; Svitacheva, Naila; Stämpfli, Martin R.; Thim, Kerstin; Smailagic, Amir; Virtala, Robert; Taylor, John D.

doi:10.1007/s00011-010-0193-5

Cited by 9 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, CCR1 serves as a receptor for a number of inflammatory chemokines and is upregulated in response to inflammatory stimuli [18][19][20]. Studies showed that CCR1 was involved in the inflammatory response to cigarette smoking in murine models [21], and it may play a critical role in the pathogenesis of COPD. Similarly, Joubert et al demonstrated that CCR1 was expressed on human airway smooth muscle cells in patients [22], which may involve in airway remodeling in asthma.…”

Section: Aging Discussionmentioning

confidence: 99%

Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway

Zhao

Dong

et al. 2020

Aging

View full text Add to dashboard Cite

INTRODUCTIONChronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and concurrent progressive airflow limitation [1][2][3]. Patients may experience episodes of exacerbated respiratory symptoms, and the frequency of exacerbations requiring hospitalization increases, resulting in significant social and economic burden and one of the major causes of morbidity and mortality worldwide [4,5]. The pathogenesis of COPD and exacerbations may be associated with inflammatory cells, including macrophages, neutrophils, and T lymphocytes [6,7]. These cells are crucial in parenchymal destruction and development of airflow limitation in patients with COPD [8,9]. Chemokines and their receptors regulate leukocyte adhesion and homing, and these receptors play a critical role in trafficking of leukocytes to sites of injury and www.aging-us.com

show abstract

Section: Aging Discussionmentioning

confidence: 99%

Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway

Zhao

Dong

et al. 2020

Aging

View full text Add to dashboard Cite

show abstract

“…Several groups, using knock-out and transgenic mice, have clearly demonstrated the importance of multiple genes and pathways, including chemokine/cytokine receptors (e.g. C–C motif receptor (CCR)1, CCR5, CCR6 [ 12 – 14 ]), metalloproteinase enzymes (e.g. MMP-9/12 [ 15 ]), cytokines (e.g.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional profiling and targeted proteomics reveals common molecular changes associated with cigarette smoke-induced lung emphysema development in five susceptible mouse strains

et al. 2015

View full text Add to dashboard Cite

BackgroundMouse models are useful for studying cigarette smoke (CS)-induced chronic pulmonary pathologies such as lung emphysema. To enhance translation of large-scale omics data from mechanistic studies into pathophysiological changes, we have developed computational tools based on reverse causal reasoning (RCR).ObjectiveIn the present study we applied a systems biology approach leveraging RCR to identify molecular mechanistic explanations of pathophysiological changes associated with CS-induced lung emphysema in susceptible mice.Methods The lung transcriptomes of five mouse models (C57BL/6, ApoE−/−, A/J, CD1, and Nrf2−/−) were analyzed following 5–7 months of CS exposure.Results We predicted 39 molecular changes mostly related to inflammatory processes including known key emphysema drivers such as NF-κB and TLR4 signaling, and increased levels of TNF-α, CSF2, and several interleukins. More importantly, RCR predicted potential molecular mechanisms that are less well-established, including increased transcriptional activity of PU.1, STAT1, C/EBP, FOXM1, YY1, and N-COR, and reduced protein abundance of ITGB6 and CFTR. We corroborated several predictions using targeted proteomic approaches, demonstrating increased abundance of CSF2, C/EBPα, C/EBPβ, PU.1, BRCA1, and STAT1.Conclusion These systems biology-derived candidate mechanisms common to susceptible mouse models may enhance understanding of CS-induced molecular processes underlying emphysema development in mice and their relevancy for human chronic obstructive pulmonary disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s00011-015-0820-2) contains supplementary material, which is available to authorized users.

show abstract

“…In particular, CS has been used extensively to investigate mechanisms of COPD pathogenesis since it is the major risk factor in the development of COPD [ 3 ]. While whole body exposure to CS for a short-term (3 days to 4 weeks) has been useful in evaluating the mechanisms of CS-induced acute lung inflammation and defective innate immune responses to subsequent infections [ 4 - 7 ], long-term exposure to CS for periods up to 6 months has been employed to understand the mechanisms of emphysema development [ 8 - 11 ]. However, neither of these models show changes in small airways, which plays a major role in the development of airflow limitation in COPD implying that other factors in addition to CS are required to mimic COPD lung disease in mice [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Combined exposure to cigarette smoke and nontypeable Haemophilus influenzae drives development of a COPD phenotype in mice

et al. 2014

View full text Add to dashboard Cite

BackgroundCigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD). CS-exposed mice develop emphysema and mild pulmonary inflammation but no airway obstruction, which is also a prominent feature of COPD. Therefore, CS may interact with other factors, particularly respiratory infections, in the pathogenesis of airway remodeling in COPD.MethodsC57BL/6 mice were exposed to CS for 2 h a day, 5 days a week for 8 weeks. Mice were also exposed to heat-killed non-typeable H. influenzae (HK-NTHi) on days 7 and 21. One day after the last exposure to CS, mice were sacrificed and lung inflammation and mechanics, emphysematous changes, and goblet cell metaplasia were assessed. Mice exposed to CS or HK-NTHi alone or room air served as controls. To determine the susceptibility to viral infections, we also challenged these mice with rhinovirus (RV).ResultsUnlike mice exposed to CS or HK-NTHi alone, animals exposed to CS/HK-NTHi developed emphysema, lung inflammation and goblet cell metaplasia in both large and small airways. CS/HK-NTHi-exposed mice also expressed increased levels of mucin genes and cytokines compared to mice in other groups. CS/HK-NTHi-exposed mice infected with RV demonstrated increased viral persistence, sustained neutrophilia, and further increments in mucin gene and chemokine expression compared to other groups.ConclusionsThese findings indicate that in addition to CS, bacteria may also contribute to development of COPD, particularly changes in airways. Mice exposed to CS/HK-NTHi are also more susceptible to subsequent viral infection than mice exposed to either CS or HK-NTHi alone.

show abstract

The role of the CCR1 receptor in the inflammatory response to tobacco smoke in a mouse model

Cited by 9 publications

References 40 publications

Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway

Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway

Transcriptional profiling and targeted proteomics reveals common molecular changes associated with cigarette smoke-induced lung emphysema development in five susceptible mouse strains

Combined exposure to cigarette smoke and nontypeable Haemophilus influenzae drives development of a COPD phenotype in mice

Contact Info

Product

Resources

About