Faculty Opinions recommendation of Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3β.

Prostanoids may be involved in bradykinin (BK)-induced bronchoconstriction in asthma. We investigated whether cyclooxygenase (COX)-2 induction was involved in prostaglandin (PG) E2 release by BK in cultured human airway smooth muscle (ASM) cells and analyzed the BK receptor subtypes responsible. BK stimulated PGE2release, COX activity, and COX-2 induction in a concentration- and time-dependent manner. It also time dependently enhanced arachidonic acid release. In short-term (15-min) experiments, BK stimulated PGE2 generation but did not increase COX activity or induce COX-2. In long-term (4-h) experiments, BK enhanced PGE2 release and COX activity and induced COX-2. The long-term responses were inhibited by the protein synthesis inhibitors cycloheximide and actinomycin D and the steroid dexamethasone. The effects of BK were mimicked by the B2-receptor agonist [Tyr(Me)8]BK, whereas the B1 agonist des-Arg9-BK was weakly effective at high concentrations. The B2antagonist HOE-140 potently inhibited all the effects, but the B1 antagonist des-Arg9,(Leu8)-BK was inactive. This study is the first to demonstrate that BK can induce COX-2. Conversion of increased arachidonic acid release to PGE2 by COX-1 is mainly involved in the short-term effect, whereas B2 receptor-related COX-2 induction is important in the long-term PGE2 release.

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A human airway smooth muscle cell line that retains physiological responsiveness

AJP Cell Physiology ◽

10.1152/ajpcell.1989.256.2.c329 ◽

1989 ◽

Vol 256 (2) ◽

pp. C329-C335 ◽

Cited By ~ 245

Author(s):

R. A. Panettieri ◽

R. K. Murray ◽

L. R. DePalo ◽

P. A. Yadvish ◽

M. I. Kotlikoff

Keyword(s):

Smooth Muscle ◽

Cell Line ◽

Airway Smooth Muscle ◽

Cytosolic Calcium ◽

Airway Smooth Muscle Cell ◽

Airway Smooth Muscle Cells ◽

Functional Coupling ◽

Functional Responses ◽

Human Airway Smooth Muscle ◽

Human Airway

We report the development of a nontransformed line of human airway smooth muscle cells retaining smooth muscle-specific contractile protein expression and physiological responsiveness to agonists implicated in inflammatory airway diseases. Specific responses to histamine, leukotrienes, bradykinin, platelet-activating factor, substance P, and thromboxane analogues are demonstrated as well as functional coupling to beta-adrenergic receptors. The cell line was characterized using indirect immunofluorescence, as well as electrophoretic separation and immunoblot analysis of smooth muscle-specific actin. Functional responses were assessed by measurements of cytosolic calcium and stimulation of adenosine 3',5'-cyclic monophosphate production. The cells retain their responsiveness over many population doublings and should be a useful model to examine specific receptor-effector mechanisms, as well as the effects of neurohumoral agents on the regulation of airway smooth muscle growth and differentiation.

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TNFα and IFNγ Phosphorylate RNA Polymerase II To Synergistically Enhance CXCL-10 Release from Human Airway Smooth Muscle Cells.

10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a6312 ◽

2009 ◽

Author(s):

DL Clarke ◽

S Jindarat ◽

D Proud ◽

L Corbett ◽

L Pang ◽

...

Keyword(s):

Smooth Muscle ◽

Rna Polymerase ◽

Smooth Muscle Cells ◽

Rna Polymerase Ii ◽

Airway Smooth Muscle ◽

Muscle Cells ◽

Airway Smooth Muscle Cells ◽

Human Airway Smooth Muscle ◽

Human Airway

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FFAR1 activation attenuates histamine-induced myosin light chain phosphorylation and cortical tension development in human airway smooth muscle cells

Respiratory Research ◽

10.1186/s12931-020-01584-w ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Shengjie Xu ◽

Anthony Schwab ◽

Nikhil Karmacharya ◽

Gaoyuan Cao ◽

Joanna Woo ◽

...

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Light Chain ◽

Myosin Light Chain ◽

Airway Hyperreactivity ◽

Human Airway Smooth Muscle ◽

Tension Development ◽

Cortical Tension ◽

Human Airway ◽

Mlc Phosphorylation

Abstract Background Activation of free fatty acid receptors (FFAR1 and FFAR4) which are G protein-coupled receptors (GPCRs) with established (patho)physiological roles in a variety of obesity-related disorders, induce human airway smooth muscle (HASM) cell proliferation and shortening. We reported amplified agonist-induced cell shortening in HASM cells obtained from obese lung donors. We hypothesized that FFAR1 modulate excitation–contraction (EC) coupling in HASM cells and play a role in obesity-associated airway hyperresponsiveness. Methods In HASM cells pre-treated (30 min) with FFAR1 agonists TAK875 and GW9508, we measured histamine-induced Ca2+ mobilization, myosin light chain (MLC) phosphorylation, and cortical tension development with magnetic twisting cytometry (MTC). Phosphorylation of MLC phosphatase and Akt also were determined in the presence of the FFAR1 agonists or vehicle. In addition, the effects of TAK875 on MLC phosphorylation were measured in HASM cells desensitized to β2AR agonists by overnight salmeterol treatment. The inhibitory effect of TAK875 on MLC phosphorylation was compared between HASM cells from age and sex-matched non-obese and obese human lung donors. The mean measurements were compared using One-Way ANOVA with Dunnett’s test for multiple group comparisons or Student’s t-test two-group comparison. For cortical tension measurements by magnetic twisted cytometry, mixed effect model using SAS V.9.2 was applied. Means were considered significant when p ≤ 0.05. Results Unexpectedly, we found that TAK875, a synthetic FFAR1 agonist, attenuated histamine-induced MLC phosphorylation and cortical tension development in HASM cells. These physiological outcomes were unassociated with changes in histamine-evoked Ca2+ flux, protein kinase B (AKT) activation, or MLC phosphatase inhibition. Of note, TAK875-mediated inhibition of MLC phosphorylation was maintained in β2AR-desensitized HASM cells and across obese and non-obese donor-derived HASM cells. Conclusions Taken together, our findings identified the FFAR1 agonist TAK875 as a novel bronchoprotective agent that warrants further investigation to treat difficult-to-control asthma and/or airway hyperreactivity in obesity.

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