ArticleAmerican journal of respiratory cell and molecular biology2026
Oxidized phosphatidylcholines inhibit airway smooth muscle β2-adrenergic receptors via protein kinase C.
Article in American journal of respiratory cell and molecular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
- Commented on by
Authors and funding
13 authors.
Funding
Abstract
Understanding mechanisms for β2 adrenergic receptor (β2AR) insensitivity in asthma is incomplete. We discovered that the accumulation of oxidized phosphatidylcholines (OxPCs) in the lung correlates with airway hyperresponsiveness and that OxPCs induce contraction and cytokine synthesis in human airway smooth muscle (HASM) cells. Here, we test whether OxPCs impair β2AR agonist bronchodilator responses and related mechanism(s) for β2AR insensitivity. Using tracheal rings from BALB/c mice, we assayed the effects of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) on β2AR agonist (isoproterenol [Iso])-induced relaxation of methacholine-contracted airways. OxPAPC preexposure attenuated Iso-induced airway relaxation, increasing Iso half-maximal effective concentration (EC50) 4.3-fold and reducing maximum relaxation by 12.2%. OxPAPC did not affect adenylyl cyclase-mediated relaxation induced by forskolin. OxPAPC significantly inhibited Iso-induced bronchodilation in murine precision-cut lung slices. Intranasal OxPAPC prechallenge significantly inhibited albuterol-mediated suppression of methacholine-induced respiratory resistance in BALB/c mice. In cultured HASM cells, OxPAPC dose-dependently inhibited Iso (but not forskolin)-induced phosphorylation of the protein kinase A substrate VASP by up to 53%. Live cell cyclic adenosine monophosphate (cAMP) difference detector in situ assay for intracellular cAMP confirmed that OxPAPC dose-dependently reduces Iso-elicited cAMP generation up to 50%. OxPAPC did not reduce the abundance of cell surface hemagglutinin-tagged human β2AR in HEK293 cells. However, inhibition of protein kinase C prevented the suppressive effects of OxPAPC on both Iso-induced relaxation of murine tracheal rings and cAMP signaling in cultured HASM cells. In summary, OxPAPC impairs β2AR agonist-induced bronchodilation by PKC-dependent suppression of β2AR-mediated cAMP signaling upstream of adenylyl cyclase in HASM cells. These observations reveal a new mechanism for bronchodilator insensitivity.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.