Bradykinin in asthma: Modulation of airway inflammation and remodelling

Ricciardolo, Fabio Luigi Massimo; Folkerts, Gert; Folino, Anna; Mognetti, Barbara

doi:10.1016/j.ejphar.2018.03.017

Cited by 40 publications

(37 citation statements)

References 99 publications

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“…We observe asthma exacerbations that occur in the absence of a virus are characterized by induction of keratinization, epithelial barrier pathways, and tissue kallikreins, which may represent metaplasia of the epithelium towards keratinized squamous cells as observed with noxious exposures such as cigarette smoke 39 . Kallikreins generate kinins, including bradykinin, a key mediator of multiple acute responses in asthma that also impacts airway remodeling 40, 41 . Importantly, our findings directly relate features of airway epithelial barrier dysfunction to epithelial kallikrein induction in asthma exacerbations.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children

et al. 2019

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Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation. We show an additional set of multiple inflammatory cell pathways involved in virus-associated exacerbations, in contrast to squamous cell pathways associated with nonviral exacerbations. Our work introduces an in vivo molecular platform to investigate, in a clinical setting, both the mechanisms of disease pathogenesis and therapeutic targets to modify exacerbations.

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Section: Discussionmentioning

confidence: 99%

Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children

et al. 2019

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“…One of the keystone recent discoveries demonstrated a direct link between sphingolipid signalling and trauma/inflammation-provoked responses in muscle progenitor cells[ 67 ]. Bradykinin and its related peptides are pro-inflammatory molecules and muscle-specific growth factors that mediate exudative and inflammatory phases of muscle healing[ 69 , 70 ]. Bradykinin is also the leading member of the kinin/kallikrein system, which directs inflammation-linked responses in mesenchymal cells including fibroblasts, myofibroblasts, and smooth muscle cells[ 70 ].…”

Section: Sphk/s1p/s1p Receptors Signalling In Muscle Stem/progenitor mentioning

confidence: 99%

“…Bradykinin and its related peptides are pro-inflammatory molecules and muscle-specific growth factors that mediate exudative and inflammatory phases of muscle healing[ 69 , 70 ]. Bradykinin is also the leading member of the kinin/kallikrein system, which directs inflammation-linked responses in mesenchymal cells including fibroblasts, myofibroblasts, and smooth muscle cells[ 70 ]. Bradykinin has been shown to induce myogenic differentiation in C2C12 myoblasts through SphK1, the specific S1P-transporter spinster homolog 2 (Spns2), and S1P2 receptor.…”

Section: Sphk/s1p/s1p Receptors Signalling In Muscle Stem/progenitor mentioning

confidence: 99%

Regulatory role of sphingosine kinase and sphingosine-1-phosphate receptor signaling in progenitor/stem cells

Ng¹,

Yarla²,

Menschikowski³

et al. 2018

WJSC

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Balanced sphingolipid signaling is important for the maintenance of homeostasis. Sphingolipids were demonstrated to function as structural components, second messengers, and regulators of cell growth and survival in normal and disease-affected tissues. Particularly, sphingosine kinase 1 (SphK1) and its product sphingosine-1-phosphate (S1P) operate as mediators and facilitators of proliferation-linked signaling. Unlimited proliferation (self-renewal) within the regulated environment is a hallmark of progenitor/stem cells that was recently associated with the S1P signaling network in vasculature, nervous, muscular, and immune systems. S1P was shown to regulate progenitor-related characteristics in normal and cancer stem cells (CSCs) via G-protein coupled receptors S1Pn (n = 1 to 5). The SphK/S1P axis is crucially involved in the regulation of embryonic development of vasculature and the nervous system, hematopoietic stem cell migration, regeneration of skeletal muscle, and development of multiple sclerosis. The ratio of the S1P receptor expression, localization, and specific S1P receptor-activated downstream effectors influenced the rate of self-renewal and should be further explored as regeneration-related targets. Considering malignant transformation, it is essential to control the level of self-renewal capacity. Proliferation of the progenitor cell should be synchronized with differentiation to provide healthy lifelong function of blood, immune systems, and replacement of damaged or dead cells. The differentiation-related role of SphK/S1P remains poorly assessed. A few pioneering investigations explored pharmacological tools that target sphingolipid signaling and can potentially confine and direct self-renewal towards normal differentiation. Further investigation is required to test the role of the SphK/S1P axis in regulation of self-renewal and differentiation.

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“…Bradykinin is implicated in several pathophysiological events, including coagulation ( Del Rosso et al, 2011 ; Wu, 2015 ; Weidmann et al, 2017 ) and thrombosis, fibrinolysis ( Del Rosso et al, 2008 ), and acute inflammation ( Kaplan and Joseph, 2014 ; Wu, 2015 ; Schmaier, 2016 ). Among the physiological functions of bradykinin is vascular permeability ( Bjorkqvist et al, 2013 ; Couture et al, 2014 ) and smooth-muscle contractility ( Ricciardolo et al, 2018 ). It is possible that bradykinin, acting via BDKR-B1 and/or -B2, mediates increased tissue hydration in the cervix during ripening by altering endothelial cell junctions ( Couture et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Progesterone Receptor Signaling Selectively Modulates Cytokine-Induced Global Gene Expression in Human Cervical Stromal Cells

Kniss

Summerfield

2020

Front. Genet.

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Preterm birth (PTB) is the leading cause of morbidity and mortality in infants <1 year of age. Intrauterine inflammation is a hallmark of preterm and term parturition; however, this alone cannot fully explain the pathobiology of PTB. For example, the cervix undergoes a prolonged series of biochemical and biomechanical events, including extracellular matrix (ECM) remodeling and mechanochemical changes, culminating in ripening. Vaginal progesterone (P 4) prophylaxis demonstrates great promise in preventing PTB in women with a short cervix (<25 mm). We used a primary culture model of human cervical stromal fibroblasts to investigate gene expression signatures in cells treated with interleukin-1β (IL-1β) in the presence or absence of P 4 following 17βestradiol (17β-E 2) priming for 7-10 days. Microarrays were used to measure global gene expression in cells treated with cytokine or P 4 alone or in combination, followed by validation of select transcripts by semiquantitative polymerase chain reactions (qRT-PCR). Primary/precursor (MIR) and mature microRNAs (miR) were quantified by microarray and NanoString R platforms, respectively, and validated by qRT-PCR. Differential gene expression was computed after data normalization followed by pathway analysis using Kyoto Encyclopedia Genes and Genomes (KEGG), Panther, Gene Ontology (GO), and Ingenuity Pathway Analysis (IPA) upstream regulator algorithm tools. Treatment of fibroblasts with IL-1β alone resulted in the differential expression of 1432 transcripts (protein coding and non-coding), while P 4 alone led to the expression of only 43 transcripts compared to untreated controls. Cytokines, chemokines, and their cognate receptors and prostaglandin endoperoxide synthase-2 (PTGS-2) were among the most highly upregulated transcripts following either IL-1β or IL-1β + P 4. Other prominent differentially expressed transcripts were those encoding ECM proteins, ECMdegrading enzymes, and enzymes involved in glycosaminoglycan (GAG) biosynthesis. We also detected differential expression of bradykinin receptor-1 and-2 transcripts, suggesting (prominent in tissue injury/remodeling) a role for the kallikrein-kinin system

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Bradykinin in asthma: Modulation of airway inflammation and remodelling

Cited by 40 publications

References 99 publications

Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children

Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children

Regulatory role of sphingosine kinase and sphingosine-1-phosphate receptor signaling in progenitor/stem cells

Progesterone Receptor Signaling Selectively Modulates Cytokine-Induced Global Gene Expression in Human Cervical Stromal Cells

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