Airway smooth muscle as an immunomodulatory cell

Pulmonary, Allergy and Critical Care Division, Airways Biology Initiative, University of Pennsylvania, Philadelphia, PA 19104-3403, USA.
Pulmonary Pharmacology &amp Therapeutics (Impact Factor: 2.94). 01/2002; 22(5). DOI: 10.1016/j.pupt.2008.12.006
Source: OAI


Although pivotal in regulating bronchomotor tone in asthma, airway smooth muscle (ASM) also modulates airway inflammation in asthma. ASM myocytes secrete or express a wide array of immunomodulatory mediators in response to extracellular stimuli, and in chronic severe asthma, increases in ASM mass may also render the airway irreversibly obstructed. Although the mechanisms by which ASM secretes cytokines and chemokines are shared with those regulating immune cells, there exist unique ASM signaling pathways that may provide novel therapeutic targets. This review provides an overview of our current understanding of the proliferative as well as synthetic properties of ASM.

2 Reads
  • Source
    • "These gaps in knowledge are largely due to the lack of methodologies that allow direct and high fidelity isolation of bronchial smooth muscle cells (BSMCs) and vascular smooth muscle cells (VSMCs). Due to the absence of such methodologies, our current understanding of the lung smooth muscle phenotype is primarily derived from the study of in vitro cultured and passaged cells, and from the morphological and histological study of lung tissue [1]–[4]. In view of the limitations of these approaches, the precise pathophysiological differences in global gene expression, cell size, and tone between normal and diseased smooth muscle cells remain unresolved [5]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Phenotypes of lung smooth muscle cells in health and disease are poorly characterized. This is due, in part, to a lack of methodologies that allow for the independent and direct isolation of bronchial smooth muscle cells (BSMCs) and vascular smooth muscle cells (VSMCs) from the lung. In this paper, we describe the development of a bi-fluorescent mouse that permits purification of these two cell populations by cell sorting. By subjecting this mouse to an acute allergen based-model of airway inflammation that exhibits many features of asthma, we utilized this tool to characterize the phenotype of so-called asthmatic BSMCs. First, we examined the biophysical properties of single BSMCs from allergen sensitized mice and found increases in basal tone and cell size that were sustained ex vivo. We then generated for the first time, a comprehensive characterization of the global gene expression changes in BSMCs isolated from the bi-fluorescent mice with allergic airway inflammation. Using statistical methods and pathway analysis, we identified a number of differentially expressed mRNAs in BSMCs from allergen sensitized mice that code for key candidate proteins underlying changes in matrix formation, contractility, and immune responses. Ultimately, this tool will provide direction and guidance for the logical development of new markers and approaches for studying human lung smooth muscle.
    PLoS ONE 09/2013; 8(9):e74469. DOI:10.1371/journal.pone.0074469 · 3.23 Impact Factor
  • Source
    • "In the present study, we found that galangin inhibited IκBα degradation and p65 phosphorylation and nuclear translocation in an OVA-induced mouse asthma model. ASMC contribute to the pathogenesis of asthma at multiple levels beyond its contractile functions; they secrete cytokines, chemokines, and adhesion molecules, which may participate in or even perpetuate mucosal inflammatory changes via the activation and recruitment of inflammatory cells [26]. In an in vitro study, we founded that galangin reduced the expression of chemokines and adhesion molecules thorough inhibition of the NF-κB pathway in TNF-α-stimulated normal human ASMC. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Persistent activation of nuclear factor κB (NF-κB) has been associated with the development of asthma. Galangin, the active pharmacological ingredient from Alpinia galanga, is reported to have a variety of anti-inflammatory properties in vitro via negative regulation of NF-κB. This study aimed to investigate whether galangin can abrogate ovalbumin- (OVA-) induced airway inflammation by negative regulation of NF-κB. BALB/c mice sensitized and challenged with OVA developed airway hyperresponsiveness (AHR) and inflammation. Galangin dose dependently inhibited OVA-induced increases in total cell counts, eosinophil counts, and interleukin-(IL-) 4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and reduced serum level of OVA-specific IgE. Galangin also attenuated AHR, reduced eosinophil infiltration and goblet cell hyperplasia, and reduced expression of inducible nitric oxide synthase and vascular cell adhesion protein-1 (VCAM-1) levels in lung tissue. Additionally, galangin blocked inhibitor of κB degradation, phosphorylation of the p65 subunit of NF-κB, and p65 nuclear translocation from lung tissues of OVA-sensitized mice. Similarly, in normal human airway smooth muscle cells, galangin blocked tumor necrosis factor-α induced p65 nuclear translocation and expression of monocyte chemoattractant protein-1, eotaxin, CXCL10, and VCAM-1. These results suggest that galangin can attenuate ovalbumin-induced airway inflammation by inhibiting the NF-κB pathway.
    Evidence-based Complementary and Alternative Medicine 05/2013; 2013:767689. DOI:10.1155/2013/767689 · 1.88 Impact Factor
  • Source
    • "Traditionally, the interest in bronchial smooth muscle in airway diseases has concerned its contractile properties leading to airway obstruction. Although this interest remains with still unmet medical needs [24], during the last two decades the research focus has increasingly been on the synthetic and immunomodulatory properties of the bronchial smooth muscle cells (BSMCs) [25]. BSMCs thus express functional TLRs with preferential expression of TLR3 [26]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Rhinovirus (RV) infections cause exacerbations and development of severe asthma highlighting the importance of antiviral interferon (IFN) defence by airway cells. Little is known about bronchial smooth muscle cell (BSMC) production of IFNs and whether BSMCs have dsRNA-sensing receptors besides TLR3. dsRNA is a rhinoviral replication intermediate and necrotic cell effect mimic that mediates innate immune responses in bronchial epithelial cells. We have explored dsRNA-evoked IFN-β and IFN-λ1 production in human BSMCs and potential involvement of TLR3 and RIG-I-like receptors (RLRs). Primary BSMCs were stimulated with 0.1-10 µg/ml dsRNA, 0.1-1 µg/ml dsRNA in complex with the transfection agent LyoVec (dsRNA/LyoVec; selectively activating cytosolic RLRs) or infected with 0.05-0.5 MOI RV1B. Both dsRNA stimuli evoked early (3 h), concentration-dependent IFN-β and IFN-λ1 mRNA expression, which with dsRNA/LyoVec was much greater, and with dsRNA was much less, after 24 h. The effects were inhibited by dexamethasone. Further, dsRNA and dsRNA/LyoVec concentration-dependently upregulated RIG-I and MDA5 mRNA and protein. dsRNA and particularly dsRNA/LyoVec caused IFN-β and IFN-λ1 protein production (24 h). dsRNA- but not dsRNA/LyoVec-induced IFN expression was partly inhibited by chloroquine that suppresses endosomal TLR3 activation. RV1B dose-dependently increased BSMC expression of RIG-I, MDA5, IFN-β, and IFN-λ1 mRNA. We suggest that BSMCs express functional RLRs and that both RLRs and TLR3 are involved in viral stimulus-induced BSMC expression of IFN-β and IFN-λ1.
    PLoS ONE 04/2013; 8(4):e62718. DOI:10.1371/journal.pone.0062718 · 3.23 Impact Factor
Show more