scholarly journals Interleukin-33 Drives Activation of Alveolar Macrophages and Airway Inflammation in a Mouse Model of Acute Exacerbation of Chronic Asthma

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Melissa M. Bunting ◽  
Alexander M. Shadie ◽  
Rylie P. Flesher ◽  
Valentina Nikiforova ◽  
Linda Garthwaite ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Acute Exacerbation ◽  
Proinflammatory Cytokines ◽  
Alveolar Macrophages ◽  
Surface Proteins ◽  
Alternative Activation ◽  
Chronic Asthma ◽  
Activation Markers ◽  
Interleukin 33 ◽  
Enhanced Expression

We investigated the role of interleukin-33 (IL-33) in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM) were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.

scholarly journals Increased Ratio of Matrix Metalloproteinase-9 (MMP-9)/Tissue Inhibitor Metalloproteinase-1 from Alveolar Macrophages in Chronic Asthma with a Fast Decline in FEV1 at 5-Year Follow-up

2019 ◽  
Vol 8 (9) ◽  
pp. 1451 ◽  
Author(s):  
Fu-Tsai Chung ◽  
Hung-Yu Huang ◽  
Chun-Yu Lo ◽  
Yu-Chen Huang ◽  
Chang-Wei Lin ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Alveolar Macrophages ◽  
Inhaled Corticosteroids ◽  
Airway Remodeling ◽  
Bronchial Biopsy ◽  
Chronic Asthma ◽  
Tissue Inhibitor ◽  
Fev1 Decline

Chronic asthma is associated with progressive airway remodeling, which may contribute to declining lung function. An increase in matrix metalloproteinases-9 (MMP-9)/tissue inhibitor metalloproteinase-1 (TIMP-1) may indicate airway inflammation and bronchial injury. Bronchial biopsy specimens and alveolar macrophages (AMs) were obtained from patients with asthma under regular treatment with inhaled corticosteroids or combination therapy and normal subjects (n = 10). Asthmatics included those with a slow forced expiratory volume in one second (FEV1) decline (<30 mL/year, n = 13) and those with a fast FEV1 decline (≥30 mL/year, n = 8) in 5-year follow-up. Immunostaining expression of MMP-9 and TIMP-1 was detected in airway tissues. MMP-9 and TIMP-1 was measured from AMs cultured for 24 h. After the 5-year treatment, the methacholine airway hyperresponsiveness of the slow FEV1 decline group was decreased, but that of the fast FEV1 decline group was increased (PC20, provocative concentration causing a 20% decrease in FEV1, 3.12 ± 1.10 to 1.14 ± 0.34 mg/dL, p < 0.05). AMs of asthma with a fast FEV1 decline released a higher level of MMP-9 (8.52 ± 3.53 pg/mL, p < 0.05) than those of a slow FEV1 decline (0.99 ± 0.20 pg/mL). The MMP-9/TIMP ratio in the fast FEV1 decline group (0.089 ± 0.032) was higher than that of the slow FEV1 decline group (0.007 ± 0.001, p < 0.01). The annual FEV1 decline in 5 years was proportional to the level of MMP-9 (r = 57, p < 0.01) and MMP-9/TIMP-1 ratio (r = 0.58, p < 0.01). The airways of asthma with greater yearly decline in FEV1 showed an increased thickness of submucosa and strong expression of MMP-9. An increase in MMP-9 and MMP-9/TIMP-1 in airways or AMs could be indicators of chronic airway inflammation and contribute to a greater decline in lung function of patients with chronic asthma.

scholarly journals Alveolar Macrophages Stimulate Enhanced Cytokine Production by Pulmonary CD4+ T-Lymphocytes in an Exacerbation of Murine Chronic Asthma

2010 ◽  
Vol 177 (4) ◽  
pp. 1657-1664 ◽  
Author(s):  
Cristan Herbert ◽  
Melissa M. Scott ◽  
Kim H. Scruton ◽  
Rylie P. Keogh ◽  
Kristy C. Yuan ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Alveolar Macrophages ◽  
Cytokine Production ◽  
Chronic Asthma

scholarly journals Upregulation of Intercellular Adhesion Molecule 1 and Proinflammatory Cytokines by the Major Surface Proteins of Treponema maltophilum and Treponema lecithinolyticum, the Phylogenetic Group IV Oral Spirochetes Associated with Periodontitis and Endodontic Infections

2005 ◽  
Vol 73 (1) ◽  
pp. 268-276 ◽  
Author(s):  
Sung-Hoon Lee ◽  
Kack-Kyun Kim ◽  
Bong-Kyu Choi
Keyword(s):  
Proinflammatory Cytokines ◽  
Group Iv ◽  
Surface Proteins ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Pdl Cells ◽  
Genes Encoding ◽  
Major Surface Proteins ◽  
Endodontic Infections ◽  
Major Surface

ABSTRACT Treponema maltophilum and Treponema lecithinolyticum belong to the group IV oral spirochetes and are associated with endodontic infections, as well as periodontitis. Recently, the genes encoding the major surface proteins (Msps) of these bacteria (MspA and MspTL, respectively) were cloned and sequenced. The amino acid sequences of these proteins showed significant similarity. In this study we analyzed the functional role of these homologous proteins in human monocytic THP-1 cells and primary cultured periodontal ligament (PDL) cells using recombinant proteins. The complete genes encoding MspA and MspTL without the signal sequence were cloned into Escherichia coli by using the expression vector pQE-30. Fusion proteins tagged with N-terminal hexahistidine (recombinant MspA [rMspA] and rMspTL) were obtained, and any possible contamination of the recombinant proteins with E. coli endotoxin was removed by using polymyxin B-agarose. Flow cytometry showed that rMspA and rMspTL upregulated the expression of intercellular adhesion molecule 1 (ICAM-1) in both THP-1 and PDL cells. Expression of proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-8, was also induced significantly in both cell types by the Msps, as determined by reverse transcription-PCR and an enzyme-linked immunosorbent assay, whereas IL-1β synthesis could be detected only in the THP-1 cells. The upregulation of ICAM-1, IL-6, and IL-8 was completely inhibited by pretreating the cells with an NF-κB activation inhibitor, l-1-tosylamido-2-phenylethyl chloromethyl ketone. This suggests involvement of NF-κB activation. The increased ICAM-1 and IL-8 expression in the THP-1 cells obtained with rMsps was not inhibited in the presence of the IL-1 receptor antagonist (IL-1ra), a natural inhibitor of IL-1. Our results show that the Msps of the group IV oral spirochetes may play an important role in amplifying the local immune response by continuous inflammatory cell recruitment and retention at an infection site by stimulation of expression of ICAM-1 and proinflammatory cytokines.

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