scholarly journals Human Lung Mast Cell Products Regulate Airway Smooth Muscle CXCL10 Levels

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
H. Alkhouri ◽  
V. Cha ◽  
K. Tong ◽  
L. M. Moir ◽  
C. L. Armour ◽  
...  
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Human Lung ◽  
Serine Protease Inhibitor ◽  
Receptor Activation ◽  
Mrna Levels ◽  
Free System ◽  
A Cell ◽  
Lung Mast Cell

In asthma, the airway smooth muscle (ASM) produces CXCL10 which may attract CXCR3+ mast/T cells to it. Our aim was to investigate the effects of mast cell products on ASM cell CXCL10 production. ASM cells from people with and without asthma were stimulated with IL-1β, TNF-α, and/or IFNγ and treated with histamine (1–100 μM) ± chlorpheniramine (H1R antagonist; 1 μM) or ranitidine (H2R antagonist; 50 μM) or tryptase (1 nM) ± leupeptin (serine protease inhibitor; 50 μM), heat-inactivated tryptase, or vehicle for 4 h or 24 h. Human lung mast cells (MC) were isolated and activated with IgE/anti-IgE and supernatants were collected after 2 h or 24 h. The supernatants were added to ASM cells for 48 h and ASM cell CXCL10 production detected using ELISA (protein) and real-time PCR (mRNA). Histamine reduced IL-1β/TNF-α-induced CXCL10 protein, but not mRNA, levels independent of H1 and H2 receptor activation, whereas tryptase and MC 2 h supernatants reduced all cytokine-induced CXCL10. Tryptase also reduced CXCL10 levels in a cell-free system. Leupeptin inhibited the effects of tryptase and MC 2 h supernatants. MC 24 h supernatants contained TNF-α and amplified IFNγ-induced ASM cell CXCL10 production. This is the first evidence that MC can regulate ASM cell CXCL10 production and its degradation. Thus MC may regulate airway myositis in asthma.

scholarly journals Bidirectional Counterregulation of Human Lung Mast Cell and Airway Smooth Muscle β2 Adrenoceptors

2015 ◽  
Vol 196 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Rebecca J. Lewis ◽  
Latifa Chachi ◽  
Chris Newby ◽  
Yassine Amrani ◽  
Peter Bradding
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Human Lung ◽  
Lung Mast Cell

The CXCL10/CXCR3 Axis Mediates Human Lung Mast Cell Migration to Asthmatic Airway Smooth Muscle

2005 ◽  
Vol 171 (10) ◽  
pp. 1103-1108 ◽  
Author(s):  
Christopher E. Brightling ◽  
Alaina J. Ammit ◽  
Davinder Kaur ◽  
Judith L. Black ◽  
Andrew J. Wardlaw ◽  
...  
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Airway Smooth Muscle ◽  
Human Lung ◽  
Asthmatic Airway ◽  
Lung Mast Cell

Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases

2012 ◽  
Vol 302 (7) ◽  
pp. L700-L710 ◽  
Author(s):  
Xiahui Tan ◽  
Najwa Khalil ◽  
Candice Tesarik ◽  
Karunasri Vanapalli ◽  
Viki Yaputra ◽  
...  
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Mrna Levels ◽  
Cell Recruitment ◽  
Tnf Α ◽  
Th1 Cytokines

In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4–8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.

scholarly journals Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement

2012 ◽  
Vol 302 (10) ◽  
pp. L1118-L1127 ◽  
Author(s):  
Yazan A. Alrashdan ◽  
Hatem Alkhouri ◽  
Emily Chen ◽  
Daniel J. Lalor ◽  
Maree Poniris ◽  
...  
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Airway Smooth Muscle ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Ifn Γ ◽  
Jnk Activation

CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix). CXCL10 mRNA and protein, JNK, NF-κB p65 phosphorylation, and Iκ-Bα protein degradation were assessed using real-time PCR, ELISA, and immunoblotting, respectively. Cytomix, IL-1β, and TNF-α induced CXCL10 mRNA expression more rapidly in asthmatic than nonasthmatic ASM cells. IL-1β and/or TNF-α combined with IFN-γ synergistically increased asthmatic ASM cell CXCL10 release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but cytomix-induced release was least affected, with only JNK and NF-κB inhibitors halving it. Notably, JNK phosphorylation was markedly less in asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect CXCL10 mRNA stability or Iκ-Bα degradation. Together, the JNK and NF-κB inhibitors completely inhibited their CXCL10 release. We concluded that, in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and CXCL10 gene expression was more rapid following cytomix stimulation. However, in both, JNK activation did not regulate early events leading to NF-κB activation. Thus JNK and NF-κB provide independent therapeutic targets for limiting CXCL10 production and mast cell migration to the ASM in asthma.

scholarly journals The human lung mast cell.

1984 ◽  
Vol 55 ◽  
pp. 259-269 ◽  
Author(s):  
S I Wasserman
Keyword(s):  
Mast Cell ◽  
Human Lung ◽  
Lung Mast Cell

scholarly journals Airway smooth muscle photorelaxation via opsin receptor activation

2019 ◽  
Vol 316 (1) ◽  
pp. L82-L93 ◽  
Author(s):  
Peter D. Yim ◽  
George Gallos ◽  
Jose F. Perez-Zoghbi ◽  
Yi Zhang ◽  
Dingbang Xu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Blue Light ◽  
Airway Smooth Muscle ◽  
Ex Vivo ◽  
Receptor Activation ◽  
Upper Airways ◽  
Peripheral Airways ◽  
Protein Receptor ◽  
Calcium Activated Potassium Channels ◽  
Precision Cut Lung Slices

Nonvisual opsin (OPN) receptors have recently been implicated in blue light-mediated photorelaxation of smooth muscle in various organs. Since photorelaxation has not yet been demonstrated in airway smooth muscle (ASM) or in human tissues, we questioned whether functional OPN receptors are expressed in mouse and human ASM. mRNA, encoding the OPN 3 receptor, was detected in both human and mouse ASM. To demonstrate the functionality of the OPN receptors, we performed wire myography of ex vivo ASM from mouse and human upper airways. Blue light-mediated relaxation of ACh-preconstricted airways was intensity and wavelength dependent (maximum relaxation at 430-nm blue light) and was inhibited by blockade of the large-conductance calcium-activated potassium channels with iberiotoxin. We further implicated OPN receptors as key mediators in functional photorelaxation by demonstrating increased relaxation in the presence of a G protein receptor kinase 2 inhibitor or an OPN chromophore (9- cis retinal). We corroborated these responses in peripheral airways of murine precision-cut lung slices. This is the first demonstration of photorelaxation in ASM via an OPN receptor-mediated pathway.

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