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A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury
Chun-Xiao Sun, … , Jurgen Schnermann, Michael R. Blackburn
Chun-Xiao Sun, … , Jurgen Schnermann, Michael R. Blackburn
Published January 3, 2005
Citation Information: J Clin Invest. 2005;115(1):35-43. https://doi.org/10.1172/JCI22656.
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Article Immunology

A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury

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Abstract

Adenosine is a signaling nucleoside that has been implicated in the regulation of asthma and chronic obstructive pulmonary disease. Adenosine signaling can serve both pro- and anti-inflammatory functions in tissues and cells. In this study we examined the contribution of A1 adenosine receptor (A1AR) signaling to the pulmonary inflammation and injury seen in adenosine deaminase–deficient (ADA-deficient) mice, which exhibit elevated adenosine levels. Experiments revealed that transcript levels for the A1AR were elevated in the lungs of ADA-deficient mice, in which expression was localized predominantly to alveolar macrophages. Genetic removal of the A1AR from ADA-deficient mice resulted in enhanced pulmonary inflammation along with increased mucus metaplasia and alveolar destruction. These changes were associated with the exaggerated expression of the Th2 cytokines IL-4 and IL-13 in the lungs, together with increased expression of chemokines and matrix metalloproteinases. These findings demonstrate that the A1AR plays an anti-inflammatory and/or protective role in the pulmonary phenotype seen in ADA-deficient mice, which suggests that A1AR signaling may serve to regulate the severity of pulmonary inflammation and remodeling seen in chronic lung diseases by controlling the levels of important mediators of pulmonary inflammation and damage.

Authors

Chun-Xiao Sun, Hays W. Young, Jose G. Molina, Jonathan B. Volmer, Jurgen Schnermann, Michael R. Blackburn

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Figure 1

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A1AR
 expression in the lungs of ADA–/–
 mice. (A) Transcript levels for...
A1AR expression in the lungs of ADA–/– mice. (A) Transcript levels for the A1AR were measured in whole lung RNA extracts from postnatal day 18 ADA-containing (ADA+) and ADA-deficient (ADA–/–) mice, using semiquantitative RT-PCR. Findings from 2 different pairs of littermates are shown. RNA extracted from the brain of an ADA+ mouse was used as a positive control, and β-actin was used as an RNA-positive control for each sample. M, DNA size ladder. Quantitative RT-PCR was used to determine the levels of A1AR transcripts in day 18 whole-lung extracts (B) or BAL cell pellets (C) from ADA+ and ADA–/– mice. Data are presented as mean percentage of β-actin transcripts ± SEM; n = 4 for each. *P – 0.05 compared to ADA+. nd, not detectable. Images show (D) lung section from a postnatal day 18 ADA+ mouse hybridized with antisense A1AR riboprobe, (E) lung section from a postnatal day 18 ADA–/– mouse hybridized with antisense A1AR riboprobe, and (F) lung section from a postnatal day 18 ADA–/– mouse hybridized with sense A1AR riboprobe. Purple represents specific hybridization; pink shows counterstained nuclei. Arrows denote alveolar macrophages. Scale bar: 10 μm

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ISSN: 0021-9738 (print), 1558-8238 (online)

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