scholarly journals The Impact of Monoclonal Antibodies on Airway Smooth Muscle Contractility in Asthma: A Systematic Review

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1281
Author(s):  
Luigino Calzetta ◽  
Marina Aiello ◽  
Annalisa Frizzelli ◽  
Giuseppina Bertorelli ◽  
Beatrice Ludovica Ritondo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Monoclonal Antibodies ◽  
Airway Smooth Muscle ◽  
Smooth Muscle Contractility ◽  
Eosinophilic Asthma ◽  
Effector Cells ◽  
Cytokines And Chemokines ◽  
Wide Range ◽  
Indirect Impacts ◽  
The Impact

Airway hyperresponsiveness (AHR) represents a central pathophysiological hallmark of asthma, with airway smooth muscle (ASM) being the effector tissue implicated in the onset of AHR. ASM also exerts pro-inflammatory and immunomodulatory actions, by secreting a wide range of cytokines and chemokines. In asthma pathogenesis, the overexpression of several type 2 inflammatory mediators including IgE, IL-4, IL-5, IL-13, and TSLP has been associated with ASM hyperreactivity, all of which can be targeted by humanized monoclonal antibodies (mAbs). Therefore, the aim of this review was to systematically assess evidence across the literature on mAbs for the treatment of asthma with respect to their impact on the ASM contractile tone. Omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab were found to be effective in modulating the contractility of the ASM and preventing the AHR, but no available studies concerning the impact of reslizumab on the ASM were identified from the literature search. Omalizumab, dupilumab, and tezepelumab can directly modulate the ASM in asthma, by specifically blocking the interaction between IgE, IL-4, and TSLP, and their receptors are located on the surface of ASM cells. Conversely, mepolizumab and benralizumab have prevalently indirect impacts against AHR by targeting eosinophils and other immunomodulatory effector cells promoting inflammatory processes. AHR has been suggested as the main treatable trait towards precision medicine in patients suffering from eosinophilic asthma, therefore, well-designed head-to-head trials are needed to compare the efficacy of those mAbs that directly target ASM contractility specifically against the AHR in severe asthma, namely omalizumab, dupilumab, and tezepelumab.

scholarly journals IL-17A Recruits Rab35 to IL-17R to Mediate PKCα-Dependent Stress Fiber Formation and Airway Smooth Muscle Contractility

2019 ◽  
Vol 202 (5) ◽  
pp. 1540-1548 ◽  
Author(s):  
Katarzyna Bulek ◽  
Xing Chen ◽  
Vandy Parron ◽  
Aparna Sundaram ◽  
Tomasz Herjan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Stress Fiber Formation

scholarly journals The impact of vitamin D on asthmatic human airway smooth muscle

2015 ◽  
Vol 10 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Sannette C. Hall ◽  
Kimberly D. Fischer ◽  
Devendra K. Agrawal
Keyword(s):  
Vitamin D ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
The Impact

Interleukin-1β-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway

2002 ◽  
Vol 283 (5) ◽  
pp. L909-L917 ◽  
Author(s):  
Z.-X. Wu ◽  
B. E. Satterfield ◽  
J. S. Fedan ◽  
R. D. Dey
Keyword(s):  
Smooth Muscle ◽  
Substance P ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Sensory Nerves ◽  
Tracheal Smooth Muscle ◽  
Fiber Density ◽  
Smooth Muscle Contractility ◽  
Neurokinin 1

Interleukin (IL)-1β causes airway inflammation, enhances airway smooth muscle responsiveness, and alters neurotransmitter expression in sensory, sympathetic, and myenteric neurons. This study examines the role of intrinsic airway neurons in airway hyperresponsiveness (AHR) induced by IL-1β. Ferrets were instilled intratracheally with IL-1β (0.3 μg/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tracheal smooth muscle contractility in vitro and substance P (SP) expression in tracheal neurons were assessed. Tracheal smooth muscle reactivity to acetylcholine (ACh) and methacholine (MCh) and smooth muscle contractions to electric field stimulation (EFS) both increased after IL-1β. The IL-1β-induced AHR was maintained in tracheal segments cultured for 24 h, a procedure that depletes SP from sensory nerves while maintaining viability of intrinsic airway neurons. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the IL-1β-induced hyperreactivity to ACh and MCh and to EFS in cultured tracheal segments. SP-containing neurons in longitudinal trunk, SP innervation of superficial muscular plexus neurons, and SP nerve fiber density in tracheal smooth muscle all increased after treatment with IL-1β. These results show that IL-1β-enhanced cholinergic airway smooth muscle contractile responses are mediated by the actions of SP released from intrinsic airway neurons.

scholarly journals VIP/PACAP Signaling as an Alternative Target During Hyperoxic Exposure in Preterm Newborns

2021 ◽  
pp. 489-499
Author(s):  
Qëndrim Thaçi ◽  
Shkëlzen Reçica ◽  
Islam Kryeziu ◽  
Vadim Mitrokhin ◽  
Andre Kamkin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Adenylate Cyclase ◽  
Airway Smooth Muscle ◽  
Smooth Muscle Relaxation ◽  
Smooth Muscle Contractility ◽  
Hyperoxic Exposure ◽  
Airway Caliber ◽  
Pituitary Adenylate Cyclase ◽  
Preterm Newborns

The use of oxygen therapy (high doses of oxygen - hyperoxia) in the treatment of premature infants results in their survival. However, it also results in a high incidence of chronic lung disease known as bronchopulmonary dysplasia, a disease in which airway hyper-responsiveness and pulmonary hypertension are well known as consequences. In our previous studies, we have shown that hyperoxia causes airway hyper-reactivity, characterized by an increased constrictive and impaired airway smooth muscle relaxation due to a reduced release of relaxant molecules such as nitric oxide, measured under in vivo and in vitro conditions (extra- and intrapulmonary) airways. In addition, the relaxation pathway of the vasoactive intestinal peptide (VIP) and/or pituitary adenylate cyclase activating peptide (PACAP) is another part of this system that plays an important role in the airway caliber. Peptide, which activates VIP cyclase and pituitary adenylate cyclase, has prolonged airway smooth muscle activity. It has long been known that VIP inhibits airway smooth muscle cell proliferation in a mouse model of asthma, but there is no data about its role in the regulation of airway and tracheal smooth muscle contractility during hyperoxic exposure of preterm newborns.

Assessment of signal transduction mechanisms regulating airway smooth muscle contractility

1992 ◽  
Vol 262 (2) ◽  
pp. L119-L139 ◽  
Author(s):  
C. M. Schramm ◽  
M. M. Grunstein
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
G Proteins ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Signal Transduction Pathways ◽  
Smooth Muscle Contractility ◽  
Membrane Reconstitution

Agonist-receptor interactions regulate airway smooth muscle tone through activation of guanine nucleotide binding proteins (G proteins) which are coupled to second-messenger pathways that mediate changes in the tissue's contractile state. Various methods have been applied to identify the structure/function characteristics of G proteins and their role in signal transduction in airway smooth muscle, including the use of exotoxins, nonhydrolyzable analogs of guanosine-triphosphate (GTP), antibodies to purified G proteins, and membrane reconstitution studies. In elucidating mechanisms of airway smooth muscle relaxation, considerable progress has been made in identifying the molecular basis for receptor/G protein coupling and other regulatory processes leading to both the activation and down-regulation of the adenylate cyclase/adenosine 3' 5'-cyclic monophosphate system. Further, with respect to airway smooth muscle contraction, various approaches have been used to evaluate the role of membrane phosphoinositide turnover and the mechanisms of action of the bifurcating signal transduction pathways associated with the production and metabolism of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol, and activation of protein kinase C. This review identifies much of the information gained to date on the above signal transduction pathways, with an emphasis placed on various methodological approaches used to determine membrane and transmembrane signaling processes in airway smooth muscle.

Use of cultured airway myocytes for study of airway smooth muscle

1995 ◽  
Vol 268 (1) ◽  
pp. L1-L11 ◽  
Author(s):  
I. P. Hall ◽  
M. Kotlikoff
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Cultured Cells ◽  
Muscle Cells ◽  
Cellular Level ◽  
Receptor Expression ◽  
Airway Smooth Muscle Cells ◽  
Wide Range ◽  
Airway Responses

Cultured airway smooth muscle cells provide a convenient model system for studying the regulation of a wide range of airway responses at the cellular level. This review describes the characteristics of cultured airway smooth muscle cells and differences that exist between cultured cells and acutely dissociated cells or muscle strips. Receptor and ion-channel expression and control of coupling in cultured airway smooth muscle are reviewed. The methodology for airway smooth muscle culture is discussed. The main advantage of using cultured airway smooth muscle cells is that studies can be performed to examine long-term control of cell responses. Studies of the regulation of receptor expression and coupling, desensitization of receptor or channel-mediated responses, or regulation of the expression of important enzymes or muscle proteins can be readily performed in cell culture. In addition, cultured airway myocytes provide a useful secondary screening system for the development of novel therapeutic agents targeted at airway receptors that are expressed upon these cells.

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