ArticleAmerican journal of physiology. Lung cellular and molecular physiology2009
Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca2+ reuptake in human airway smooth muscle.
Article in American journal of physiology. Lung cellular and molecular physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- The Impact of Corticosteroids on Human Airway Smooth Muscle Contractility and Airway Hyperresponsiveness: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- TGF-β1-induced phospholamban expression alters esophageal smooth muscle cell contraction in patients with eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2014Trial
- Integrative Roles of Pro-Inflammatory Cytokines on Airway Smooth Muscle Structure and Function in Asthma.Immunological reviews · 2025Review
- Impact of Oxidative Stress and Neuroinflammation on Sarco/Endoplasmic Reticulum CaACS pharmacology & translational science · 2025Article
- Airway smooth muscle in contractility and remodeling of asthma: potential drug target mechanisms.Expert opinion on therapeutic targets · 2023Article
- Airway smooth muscle and airway hyperresponsiveness in asthma: mechanisms of airway smooth muscle dysfunction.Minerva medica · 2022Article
- Role of airway smooth muscle cell phenotypes in airway tone and obstruction in guinea pig asthma model.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2022Article
- IgE-dependent human basophil responses are inversely associated with the sarcoplasmic reticulum CaFrontiers in immunology · 2022Article
- Review
- Reciprocal Correlations of Inflammatory and Calcium Signaling in Asthma Pathogenesis.Advances in experimental medicine and biology · 2021Article
- Sex Hormones and Lung Inflammation.Advances in experimental medicine and biology · 2021Article
- Reciprocal Correlations of Inflammatory and Calcium Signaling in Asthma Pathogenesis.Advances in experimental medicine and biology · 2021Article
- Sarcolipin Exhibits Abundant RNA Transcription and Minimal Protein Expression in Horse Gluteal Muscle.Veterinary sciences · 2020Article
- Estrogen receptors differentially regulate intracellular calcium handling in human nonasthmatic and asthmatic airway smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Mechanisms underlying TNFα-induced enhancement of force generation in airway smooth muscle.Physiological reports · 2019Article
- Shot Down Inflamed: Airway Smooth Muscle Bronchodilator Insensitivity in Cystic Fibrosis.American journal of respiratory cell and molecular biology · 2019Article
- Mitochondrial regulation of airway smooth muscle functions in health and pulmonary diseases.Archives of biochemistry and biophysics · 2019Review
- Endoplasmic Reticulum Stress and Mitochondrial Function in Airway Smooth Muscle.Frontiers in cell and developmental biology · 2019Review
- Androgen Receptor-Mediated Regulation of Intracellular Calcium in Human Airway Smooth Muscle Cells.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2019Article
- Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle (Review).International journal of molecular medicine · 2018Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Airway inflammation leads to increased intracellular Ca(2+) ([Ca(2+)](i)) levels in airway smooth muscle (ASM) cells. Sarcoplasmic reticulum Ca(2+) release and reuptake are key components of ASM [Ca(2+)](i) regulation. Ca(2+) reuptake occurs via sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA) and is regulated by the inhibitory protein phospholamban (PLB) in many cell types. In human ASM, we tested the hypothesis that inflammation increases PLB, thus inhibiting SERCA function, and leading to maintained [Ca(2+)](i) levels. Surprisingly, we found that human ASM does not express PLB protein (although mRNA is detectable). Overnight exposure to the proinflammatory cytokines TNFalpha and IL-13 did not induce PLB expression, raising the issue of how SERCA is regulated. We then found that direct SERCA phosphorylation (via CaMKII) occurs in human ASM. In fura-2-loaded human ASM cells, we found that the CaMKII antagonist KN-93 significantly slowed the rate of fall of [Ca(2+)](i) transients induced by ACh or bradykinin (in zero extracellular Ca(2+)), suggesting a role for CaMKII-mediated SERCA regulation. SERCA expression was decreased by cytokine exposure, and the rate of fall of [Ca(2+)](i) transients was slowed in cells exposed to TNFalpha and IL-13. Cytokine effects on Ca(2+) reuptake were unaffected by additional exposure to KN-93. These data indicate that in human ASM, SERCA is regulated by mechanisms such as CaMKII and that airway inflammation maintains [Ca(2+)](i) levels by decreasing SERCA expression and slowing Ca(2+) reuptake.
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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 OpenQuestion graph.