Ozone-induced airway hyperresponsiveness: roles of ROCK isoforms

Lambert, J.A.; Song, Weifeng

doi:10.1152/ajplung.00353.2015

Cited by 8 publications

(8 citation statements)

References 27 publications

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“…A useful model to explore this effect is the use of O 3 to stimulate the bronchial epithelium prior to examination of the cellular functions of adjacent fibroblasts not in direct contact of O 3 ( 29 ). O 3 is a common major component of air pollution and has been revealed in various studies to cause airway epithelial shedding, airway inflammation and airway hyperresponsiveness ( 16 , 30 ). Therefore, the aim of the present study was to co-culture HLFs with airway epithelial cells pre-stimulated with O 3 and subsequently measure the functional changes, including collagen synthesis, of the fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Effects of ozone stimulation of bronchial epithelial cells on proliferation and collagen synthesis of co‑cultured lung fibroblasts

et al. 2018

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Ozone (O3) as a major air pollutant is widely recognized for causing pathological changes of the airway system. However, it is not clear whether O3 exposure of bronchial epithelial cells (BECs) influences the proliferation and collagen synthesis of submucosal fibroblasts and contributes to the pathogenesis of airway remodeling in diseases, including asthma. In the present study, a co-culture method was applied to culture human lung fibroblasts (HLFs) with human bronchial epithelial cells (HBECs) that were pre-stimulated with O3. Following co-culture for up to 24 h, the proliferation of HLFs was measured using MTT colorimetry. Furthermore, the collagen synthesis capacity of HLFs was determined by the level of hydroxyproline. In addition, the protein expression levels of cytokines, including transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α and prostaglandin E2 (PGE2) were assessed. Results indicated that the proliferation of HLFs co-cultured with HBECs was significantly inhibited when compared with HLFs cultured alone (P<0.05). By contrast, co-culture with O3-stimulated HBECs significantly promoted the proliferation of HLFs compared with the HLFs cultured alone or those cultured with HBECs but no O3 stimulation, respectively (P<0.05 and P<0.01). Furthermore, similar effects were observed regarding the collagen synthesis capacity of HLFs co-cultured with HBECs for 24. In the supernatant, TGF-β1 concentration was continuously increased over 24 h, whereas the concentration of PGE2 increased and plateaued between 12 to 24 h and TNF-α concentration was not significantly altered during the assessed time period. To conclude, the present results suggest that O3 pre-exposure of HBECs may promote the transformation of HLFs from the typical inhibitory state into a promoting state with respect to proliferation and collagen synthesis, which may likely occur through a mechanism that influences the balance between pro- and anti-inflammatory factors, including TGF-β1 and PGE2. The present findings may improve the understanding of the mechanism involved in O3-induced airway remodeling from a novel perspective of maintenance/loss of steady-state function of the airway epithelium.

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Section: Discussionmentioning

confidence: 99%

Effects of ozone stimulation of bronchial epithelial cells on proliferation and collagen synthesis of co‑cultured lung fibroblasts

et al. 2018

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“…IP 3 has been shown to activate Ca 2ϩ influx in ASM (490) and regulate local Ca 2ϩ sparks (323), while ryanodine receptor (RyR) sensitization results in abnormal Ca 2ϩ handling (113). In terms of Ca 2ϩ sensitization, ROCK appears to be important in mediating AHR in the context of environmental exposure and obesity (265,298), while regulation of RhoA activation [via RhoGEFs (guanine nucleotide exchange factors) and RhoGAPs (GTPase activating proteins)] is an emerging (but thoroughly underexplored) area in ASM biology (46).…”

Section: Novel Regulatory Pathways In Intracellular Ca 2ϩ and Contractilitymentioning

confidence: 99%

Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease

Prakash

2016

American Journal of Physiology-Lung Cellular and Molecular Phys

109

114

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Airway structure and function are key aspects of normal lung development, growth, and aging, as well as of lung responses to the environment and the pathophysiology of important diseases such as asthma, chronic obstructive pulmonary disease, and fibrosis. In this regard, the contributions of airway smooth muscle (ASM) are both functional, in the context of airway contractility and relaxation, as well as synthetic, involving production and modulation of extracellular components, modulation of the local immune environment, cellular contribution to airway structure, and, finally, interactions with other airway cell types such as epithelium, fibroblasts, and nerves. These ASM contributions are now found to be critical in airway hyperresponsiveness and remodeling that occur in lung diseases. This review emphasizes established and recent discoveries that underline the central role of ASM and sets the stage for future research toward understanding how ASM plays a central role by being both upstream and downstream in the many interactive processes that determine airway structure and function in health and disease.

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“…Smooth muscle contraction is caused by the interaction of myosin and actin filaments, and regulated by various contractile and Ca 2+ -sensitizing proteins [ 6 , 7 ]. One possible explanation of the hyper-contraction of smooth muscle may be an up-regulation of these proteins associated with contraction.…”

Section: Introductionmentioning

confidence: 99%

Augmented Pla2g4c/Ptgs2/Hpgds axis in bronchial smooth muscle tissues of experimental asthma

2018

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RationaleAugmented smooth muscle contractility of the airways is one of the causes of airway hyperresponsiveness in asthmatics. However, the mechanism of the altered properties of airway smooth muscle cells is not well understood.ObjectivesTo identify differentially expressed genes (DEGs) related to the bronchial smooth muscle (BSM) hyper-contractility in a murine asthma model.MethodsThe ovalbumin (OA)-sensitized mice were repeatedly challenged with aerosolized OA to induce asthmatic reaction. Transcriptomic profiles were generated by microarray analysis of BSM tissues from the OA-challenged and control animals, and KEGG (Kyoto Encyclopedia of Genes and Genomes) Pathway Analysis was applied.Measurements and main resultsTension study showed a BSM hyperresponsiveness to acetylcholine (ACh) in the OA-challenged mice. A total of 770 genes were differentially expressed between the OA-challenged and control animals. Pathway analysis showed a significant change in arachidonic acid (AA) metabolism pathway in BSM tissues of the OA-challenged mice. Validation of DEGs by quantitative RT-PCR showed a significant increase in PLA2 group 4c (Pla2g4c)/COX-2 (Ptgs2)/PGD2 synthase 2 (Hpgds) axis. PGD2 level in bronchoalveolar fluids of the OA-challenged mice was significantly increased. A 24-h incubation of BSM tissues with PGD2 caused a hyperresponsiveness to ACh in naive control mice.ConclusionsAA metabolism is shifted towards PGD2 production in BSM tissues of asthma. Increased PGD2 level in the airways might be a cause of the BSM hyperresponsiveness in asthma.

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Ozone-induced airway hyperresponsiveness: roles of ROCK isoforms

Cited by 8 publications

References 27 publications

Effects of ozone stimulation of bronchial epithelial cells on proliferation and collagen synthesis of co‑cultured lung fibroblasts

Effects of ozone stimulation of bronchial epithelial cells on proliferation and collagen synthesis of co‑cultured lung fibroblasts

Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease

Augmented Pla2g4c/Ptgs2/Hpgds axis in bronchial smooth muscle tissues of experimental asthma

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