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Reciprocal Correlations of Inflammatory and Calcium Signaling in Asthma Pathogenesis

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Lung Inflammation in Health and Disease, Volume I

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1303))

Abstract

Asthma is a chronic disease characterized by airway hyperresponsiveness, which can be caused by exposure to an allergen, spasmogen, or be induced by exercise. Despite its prevalence, the exact mechanisms by which the airway becomes hyperresponsive in asthma are not fully understood. There is evidence that myosin light-chain kinase is overexpressed, with a concomitant downregulation of myosin light-chain phosphatase in the airway smooth muscle, leading to sustained contraction. Additionally, the sarco/endoplasmic reticulum ATPase may be affected by inflammatory cytokines, such as IL-4, IL-5, IL-13, and TNF-α, which are all associated with asthmatic airway inflammation. IL-13 and TNF-α seem to promote sodium/calcium exchanger 1 overexpression as well. Anyhow, the exact mechanisms beyond these dysregulations need to be clarified. Of note, multiple studies show an association between asthma and the ORMLD3 gene, opening new perspectives to future potential gene therapies. Currently, several treatments are available for asthma, although many of them have systemic side effects, or are not effective in patients with severe asthma. Furthering our knowledge on the molecular and pathophysiological mechanisms of asthma plays a pivotal role for the development of new and more targeted treatments for patients who cannot totally benefit from the current therapies.

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Abbreviations

[Ca2+]i:

Intracellular Calcium Concentration

AHR:

Airway Hyperresponsiveness

ASM/ASMC:

Airway Smooth Muscle/Airway Smooth Muscle Cell

CaMKII:

Ca2+/calmodulin-dependent protein kinase II

CICR:

Calcium-Induced Calcium Release

CRTH2:

Chemoattractant receptor-homologous molecule

DAG:

Diacylglycerol

DHPR:

Dihydropyridine Receptor

FKBP12.6:

FK-506 Binding Protein

GPCR:

G-Protein Coupled Receptor

IL:

Interleukin

IP3:

Inositol Triphosphate

KCa:

Calcium-Dependent Potassium Channel

MLCK:

Myosin Light-Chain Kinase

MLCP:

Myosin Light-Chain Phosphatase

NCX:

Sodium/Calcium Exchanger

PGD2:

Prostaglandin D2

PMCA:

Plasma Membrane Calcium ATPase

ROCK:

RhoA-kinase

ROS:

Reactive Oxygen Species

RyR:

Ryanodine Receptors

SBB:

Superficial Buffer Barrier

SERCA:

Sarco/endoplasmic Reticulum ATPase

SR:

Sarcoplasmic Reticulum

TMEM16A:

Transmembrane Protein 16A

TNF-α:

Tumor Necrosis Factor-Alpha

UPR:

Unfolded Protein Response

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Author notes

  1. Ryan Okonski and Yun-Min Zheng both made an equal contribution

Authors and Affiliations

  1. Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA

    Ryan Okonski, Yun-Min Zheng, Annarita Di Mise & Yong-Xiao Wang

  2. Department of Biosciences, Biotechnologies e Biopharmaceutics, University of Bari, Bari, Italy

    Annarita Di Mise

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  3. Annarita Di Mise
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  4. Yong-Xiao Wang
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Correspondence to Annarita Di Mise or Yong-Xiao Wang .

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  1. Department of Molecular & Cellular Physiology, Albany Medical College, Albany, NY, USA

    Yong-Xiao Wang

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Okonski, R., Zheng, YM., Di Mise, A., Wang, YX. (2021). Reciprocal Correlations of Inflammatory and Calcium Signaling in Asthma Pathogenesis. In: Wang, YX. (eds) Lung Inflammation in Health and Disease, Volume I. Advances in Experimental Medicine and Biology, vol 1303. Springer, Cham. https://doi.org/10.1007/978-3-030-63046-1_17

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