scholarly journals Study on the Critical Roles of Apoptosis in Asthma Disease

2021 ◽  
Author(s):  
Farzaneh Kianian ◽  
Mehri Kadkhodaee ◽  
Hamid Reza Sadeghipour ◽  
Behjat Seifi
Keyword(s):  
Epithelial Cells ◽  
Airway Remodeling ◽  
Inflammatory Cells ◽  
Airway Epithelial Cells ◽  
The Other ◽  
Lung Damage ◽  
Airway Epithelial ◽  
Pharmacological Interventions ◽  
Apoptotic Factors ◽  
Apoptotic Cascade

Inflammation, and remodeling in airways are the two crucial characteristics of asthma, a common respiratory disease. In asthma pathophysiology, the recruitment of granulocytes finally results in inflammation, leading to lung damage. In this regard, failure to clear inflammatory cells by programmed cell death, apoptosis will cause the prolongation of inflammation. On the other hand, in airway epithelial cells, apoptosis may occur, resulting in airway remodeling. Hence, dysregulation of apoptosis has been suggested to contribute to the development of asthma. Importantly, knowledge of the factors related to apoptotic cascade seems vital to explore various pharmacological interventions for the treatment of asthma. In this review, we highlight several important apoptotic and anti-apoptotic factors contributing either to inflammatory cells or airway epithelial cells involved in asthma pathogenesis.

scholarly journals Virus Infection-Induced Bronchial Asthma Exacerbation

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Mutsuo Yamaya
Keyword(s):  
Epithelial Cells ◽  
Viral Infection ◽  
Airway Inflammation ◽  
Bronchial Asthma ◽  
Inflammatory Mediators ◽  
Asthma Exacerbation ◽  
Viral Infections ◽  
Inflammatory Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial

Infection with respiratory viruses, including rhinoviruses, influenza virus, and respiratory syncytial virus, exacerbates asthma, which is associated with processes such as airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. In patients with viral infections and with infection-induced asthma exacerbation, inflammatory mediators and substances, including interleukins (ILs), leukotrienes and histamine, have been identified in the airway secretions, serum, plasma, and urine. Viral infections induce an accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Viral infections also enhance the production of inflammatory mediators and substances in airway epithelial cells, mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect the barrier function of the airway epithelial cells and vascular endothelial cells. Recent reports have demonstrated augmented viral production mediated by an impaired interferon response in the airway epithelial cells of asthma patients. Several drugs used for the treatment of bronchial asthma reduce viral and pro-inflammatory cytokine release from airway epithelial cells infected with viruses. Here, I review the literature on the pathogenesis of the viral infection-induced exacerbation of asthma and on the modulation of viral infection-induced airway inflammation.

scholarly journals Microbial interaction: Prevotella spp. reduce P.aeruginosa induced inflammation in Cystic Fibrosis bronchial epithelial cells

2020 ◽  
Author(s):  
Anne Bertelsen ◽  
Stuart J Elborn ◽  
Bettina Schock
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Bacterial Species ◽  
Airway Epithelial Cells ◽  
Lung Damage ◽  
Airway Epithelial ◽  
Lung Function Decline ◽  
Mapk Signalling ◽  
Microbial Environment

Abstract Background: In Cystic Fibrosis (CF) airways, mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) lead to dehydrated, thick mucus which promotes the establishment of persistent polymicrobial infections and drives chronic airways inflammation. This also predisposes the airways to further infections, a vicious, self-perpetuating cycle causing lung damage and progressive lung function decline. The airways are a poly-microbial environment, containing both aerobic and anaerobic bacterial species. Pseudomonas aeruginosa (P.aeruginosa) infections contribute to the excessive inflammatory response in CF, but the role of anaerobic Prevotella spp., frequently found in CF airways, is not known.Materials: We assessed innate immune signalling in CF airway epithelial cells in response to clinical strains of P.histicola, P.nigresens and P.aeruginosa. CFBE41o- cells were infected with P.aeruginosa (MOI 100, 2h) followed by infection with P.histicola or P.nigrescens (MOI 100, 2h). Cells were incubated under anaerobic conditions for the duration of the experiments.Results: Our study shows that P.histicola and P.nigresens can reduce the growth of P.aeruginosa and dampen the inflammatory response in airway epithelial cells. We specifically illustrate that the presence of Prevotella spp. reduces Toll-like-receptor (TLR)-4, MAPK, NF-kB(p65) signalling and cytokine release (Interleukin (IL)-6, IL-8) in mixed infections. Conclusion: Our work, for the first time, strongly indicates a relationship between P. aeruginosa and anaerobe Prevotella spp. The observed modified NF-kB and MAPK signalling provides some mechanisms of this interaction that could offer a novel therapeutic approach to combat chronic P.aeruginosa infection in people with CF.

scholarly journals Exercise Inhibits the Effects of Smoke-Induced COPD Involving Modulation of STAT3

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Maysa Alves Rodrigues Brandao-Rangel ◽  
Andre Luis Lacerda Bachi ◽  
Manoel Carneiro Oliveira-Junior ◽  
Asghar Abbasi ◽  
Adriano Silva-Renno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Collagen Fiber ◽  
Aerobic Training ◽  
Airway Remodeling ◽  
Pulmonary Inflammation ◽  
Serum Levels ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Male Mice ◽  
Lung Emphysema

Purpose. Evaluate the participation of STAT3 in the effects of aerobic exercise (AE) in a model of smoke-induced COPD. Methods. C57Bl/6 male mice were divided into control, Exe, COPD, and COPD+Exe groups. Smoke were administered during 90 days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary inflammation, systemic inflammation, the level of lung emphysema, and the airway remodeling were evaluated. Analysis of integral and phosphorylated expression of STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal leukocytes was performed. Results. AE inhibited smoke-induced accumulation of total cells (p<0.001), lymphocytes (p<0.001), and neutrophils (p<0.001) in BAL, as well as BAL levels of IL-1β (p<0.001), CXCL1 (p<0.001), IL-17 (p<0.001), and TNF-α (p<0.05), while increased the levels of IL-10 (p<0.001). AE also inhibited smoke-induced increases in total leukocytes (p<0.001), neutrophils (p<0.05), lymphocytes (p<0.001), and monocytes (p<0.01) in blood, as well as serum levels of IL-1β (p<0.01), CXCL1 (p<0.01), IL-17 (p<0.05), and TNF-α (p<0.01), while increased the levels of IL-10 (p<0.001). AE reduced smoke-induced emphysema (p<0.001) and collagen fiber accumulation in the airways (p<0.001). AE reduced smoke-induced STAT3 and phospho-STAT3 expression in airway epithelial cells (p<0.001), peribronchial leukocytes (p<0.001), and parenchymal leukocytes (p<0.001). Conclusions. AE reduces smoke-induced COPD phenotype involving STAT3.

scholarly journals Host Defense and the Airway Epithelium: Frontline Responses That Protect against Bacterial Invasion and Pneumonia

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Nicholas A. Eisele ◽  
Deborah M. Anderson
Keyword(s):  
Epithelial Cells ◽  
Host Defense ◽  
Immune Cells ◽  
Airway Epithelium ◽  
Inflammatory Cells ◽  
Airway Epithelial Cells ◽  
Bacterial Invasion ◽  
Airway Epithelial ◽  
First Line ◽  
Protein Matrices

Airway epithelial cells are the first line of defense against invading microbes, and they protect themselves through the production of carbohydrate and protein matrices concentrated with antimicrobial products. In addition, they act as sentinels, expressing pattern recognition receptors that become activated upon sensing bacterial products and stimulate downstream recruitment and activation of immune cells which clear invading microbes. Bacterial pathogens that successfully colonize the lungs must resist these mechanisms or inhibit their production, penetrate the epithelial barrier, and be prepared to resist a barrage of inflammation. Despite the enormous task at hand, relatively few virulence factors coordinate the battle with the epithelium while simultaneously providing resistance to inflammatory cells and causing injury to the lung. Here we review mechanisms whereby airway epithelial cells recognize pathogens and activate a program of antibacterial pathways to prevent colonization of the lung, along with a few examples of how bacteria disrupt these responses to cause pneumonia.

scholarly journals Epithelial Immunomodulation by Aerosolized Toll-like Receptor Agonists Attenuates Allergic Responsiveness in Mice

2021 ◽  
Author(s):  
David L Goldblatt ◽  
Gabriella Valverde Ha ◽  
Shradha Wali ◽  
Vikram V Kulkarni ◽  
Michael K Longmire ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Allergen Immunotherapy ◽  
Airway Remodeling ◽  
Allergic Sensitization ◽  
Airway Epithelial Cells ◽  
The Body ◽  
Immunomodulatory Effect ◽  
Airway Epithelial ◽  
Receptor Agonists

Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness (AHR), and airway remodeling. Epidemiologic data has revealed that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells can sense allergens via myriad expression of Toll-like receptors (TLRs) and other pattern-recognition receptors (PRRs). We sought to determine whether the innate immune response stimulated by a combination of Pam2CSK4 ('Pam2', TLR2/6 ligand) and a class C oligodeoxynucleotide ODN362 ('ODN', TLR9 ligand) when delivered together by aerosol ('Pam2ODN'), can modulate the allergic immune response to allergens. Treatment with Pam2ODN 7 days before sensitization to House Dust Mite (HDM) extract resulted in a strong reduction in eosinophilic and lymphocytic inflammation. This Pam2ODN immunomodulatory effect was also seen using Ovalbumin (OVA) and A. oryzae mouse models. The immunomodulatory effect was observed as much as 30 days before sensitization to HDM, but ineffective just 2 days after sensitization, suggesting that Pam2ODN mechanism of action involves immunomodulation of the response from airway epithelial cells to aeroallergens, possibly due to a repolarization of the immune response from type 2 to a type 3/type 17 direction. Furthermore, Pam2 and ODN cooperated synergistically to induce the immunomodulatory phenotype suggesting that this treatment is superior to all investigational TLR receptor agonists in the allergen immunotherapy setting which only utilize a single PRR agonist at one time. These data suggest that allergen immunotherapy using Pam2ODN might have a role in maximizing allergen immunotherapy effectiveness.

scholarly journals Syndecan-1 Amplifies Ovalbumin-Induced Airway Remodeling by Strengthening TGFβ1/Smad3 Action

2021 ◽  
Vol 12 ◽  
Author(s):  
Dong Zhang ◽  
Xin-rui Qiao ◽  
Wen-Jing Cui ◽  
Jin-tao Zhang ◽  
Yun Pan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Remodeling ◽  
Airway Epithelial Cells ◽  
Collagen I ◽  
Chronic Asthma ◽  
Airway Epithelial ◽  
Protein Levels ◽  
Rna Targeting

Syndecan-1 (SDC-1) is a transmembrane proteoglycan of heparin sulfate that can regulate various cell signal transduction pathways in the airway epithelial cells and fibroblasts. Airway epithelial cells and human bronchial fibroblasts are crucial in airway remodeling. However, the importance of SDC-1 in the remodeling of asthmatic airways has not been confirmed yet. The present study was the first to uncover SDC-1 overexpression in the airways of humans and mice with chronic asthma. This study also validated that an increase in SDC-1 expression was correlated with TGFβ1/Smad3-mediated airway remodeling in vivo and in vitro. A small interfering RNA targeting SDC-1 (SDC-1 siRNA) and homo-SDC-1 in pcDNA3.1 (pc-SDC-1) was designed to assess the effects of SDC-1 on TGFβ1/Smad3-mediated collagen I expression in Beas-2B (airway epithelial cells) and HLF-1 (fibroblasts) cells. Downregulation of the SDC-1 expression by SDC-1 siRNA remarkably attenuated TGFβ1-induced p-Smad3 levels and collagen I expression in Beas-2B and HLF-1 cells. In addition, SDC-1 overexpression with pc-SDC-1 enhanced TGFβ1-induced p-Smad3 level and collagen I expression in Beas-2B and HLF-1 cells. Furthermore, the levels of p-Smad3 and collagen I induced by TGFβ1 were slightly increased after the addition of the recombinant human SDC-1 protein to Beas-2B and HLF-1 cells. These findings in vitro were also confirmed in a mouse model. A short hairpin RNA targeting SDC-1 (SDC-1 shRNA) to interfere with SDC-1 expression considerably reduced the levels of p-Smad3 and remodeling protein (α-SMA, collagen I) in the airways induced by ovalbumin (OVA). Similarly, OVA-induced p-Smad3 and remodeling protein levels in airways increased after mice inhalation with the recombinant mouse SDC-1 protein. These results suggested that SDC-1 of airway epithelial cells and fibroblasts plays a key role in the development of airway remodeling in OVA-induced chronic asthma.

scholarly journals Roxithromycin Inhibits Cytokine Production by and Neutrophil Attachment to Human Bronchial Epithelial Cells In Vitro

1998 ◽  
Vol 42 (6) ◽  
pp. 1499-1502 ◽  
Author(s):  
Shin Kawasaki ◽  
Hajime Takizawa ◽  
Takayuki Ohtoshi ◽  
Naonobu Takeuchi ◽  
Tadashi Kohyama ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cytokine Production ◽  
Inflammatory Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Airway Diseases ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Local Recruitment

ABSTRACT We evaluated the effect of roxithromycin on cytokine production and neutrophil attachment to human airway epithelial cells. Roxithromycin suppressed production of interleukin 8 (IL-8), IL-6, and granulocyte-macrophage colony-stimulating factor. It inhibited neutrophil adhesion to epithelial cells. Roxithromycin modulates local recruitment and activation of inflammatory cells, which may have relevance to its efficacy in airway diseases.

TNF-alpha and IL-1 beta upregulate nitric oxide-dependent ciliary motility in bovine airway epithelium

1995 ◽  
Vol 268 (6) ◽  
pp. L911-L917 ◽  
Author(s):  
B. Jain ◽  
I. Rubinstein ◽  
R. A. Robbins ◽  
J. H. Sisson
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelium ◽  
Beat Frequency ◽  
Inflammatory Cells ◽  
Ciliary Beat Frequency ◽  
Airway Epithelial Cells ◽  
Tnf Alpha ◽  
Airway Epithelial ◽  
No Donor ◽  
Ciliary Motility

Airway epithelial cells can be modulated by cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta that are released from inflammatory cells. Since ciliary motility is an important host defense function of airway epithelium, we hypothesized that cytokines, released from lung macrophages, upregulate ciliary motility. To test this hypothesis, ciliary beat frequency (CBF) was measured by video microscopy in cultured ciliated bovine bronchial epithelial cells (BBECs) incubated for 24 h with bovine alveolar macrophage-conditioned medium (AM-CM). Exposure to AM-CM resulted in a delayed (> or = 2 h) increase in CBF that was maximal after 24 h exposure (13.70 +/- 0.43 for AM-CM vs. 9.44 +/- 0.24 Hz for medium; P < 0.0001) and which was largely blocked by either anti-TNF-alpha or anti-IL-1 beta antibodies. rTNF-alpha or rIL-1 beta similarly increased CBF, which could be blocked by preincubation with either anti-rTNF-alpha or anti-rIL-1 beta antibodies. Preincubation of BBECs with actinomycin D or dexamethasone also blocked rTNF-alpha- and rIL-1 beta-induced cilia stimulation, suggesting that new protein synthesis is required for cytokine-induced upregulation of CBF. Since NO is known to upregulate ciliary motility and cytokines can induce NO synthase (NOS), we hypothesized that TNF-alpha and IL-1 beta increase CBF by inducing NOS in BBECs. The cilia stimulatory effects of TNF-alpha or IL-1 beta were inhibited by NG-monomethyl-L-arginine, a competitive NOS inhibitor, and restored by the addition of either L-arginine, an NOS substrate, or sodium nitroprusside, an NO donor.(ABSTRACT TRUNCATED AT 250 WORDS)

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