Pneumococcal infection of respiratory cells exposed to welding fumes; Role of oxidative stress and HIF-1 alpha

Grigg, Jonathan; Miyashita, Lisa; Suri, Reetika

doi:10.1371/journal.pone.0173569

Cited by 21 publications

(18 citation statements)

References 28 publications

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“…HIF-1α is implicated in mediating oxidative stress-induced PAFR expression in cultured respiratory epithelial cells (A549 and BEAS-2B) stimulated with welding fumes. 64 Fumes significantly increased ROS burden, and HIF-1α and PAFR expression, as well as S. pneumoniae infection. In unexposed cells, HIF-1α knockdown (via HIF-1α siRNA using lipofectamine) reduced PAFR expression, and HIF-1α overexpression (transfection of cultured cells with HIF-1α plasmid containing a hygromycin B resistance gene) increased PAFR expression.…”

Section: Hif-1α-induced Pafr-mediated Bacterial Infections In Copdmentioning

confidence: 91%

“…Recently, the role of HIF‐1α in regulating PAFR were also reported in the lung. HIF‐1α is implicated in mediating oxidative stress‐induced PAFR expression in cultured respiratory epithelial cells (A549 and BEAS‐2B) stimulated with welding fumes . Fumes significantly increased ROS burden, and HIF‐1α and PAFR expression, as well as S. pneumoniae infection.…”

Section: Hif‐1α‐induced Pafr‐mediated Bacterial Infections In Copdmentioning

confidence: 99%

“…Fumes significantly increased ROS burden, and HIF‐1α and PAFR expression, as well as S. pneumoniae infection. In unexposed cells, HIF‐1α knockdown (via HIF‐1α siRNA using lipofectamine) reduced PAFR expression, and HIF‐1α overexpression (transfection of cultured cells with HIF‐1α plasmid containing a hygromycin B resistance gene) increased PAFR expression . However, S. pneumoniae infection was increased in HIF‐1α‐depleted cells and remained unaltered in HIF‐1α overexpressing cells.…”

Section: Hif‐1α‐induced Pafr‐mediated Bacterial Infections In Copdmentioning

confidence: 99%

“…However, S. pneumoniae infection was increased in HIF‐1α‐depleted cells and remained unaltered in HIF‐1α overexpressing cells. Thus, HIF‐1α may also mediate S. pneumoniae infection independent of PAFR in unstimulated respiratory cells . Although both HIF‐1α levels and increased susceptibility of COPD patients to bacterial infections are regulated by NF‐κB, the mechanisms that increase the susceptibility of hypoxic COPD patients to infection are incompletely understood (Fig.…”

Section: Hif‐1α‐induced Pafr‐mediated Bacterial Infections In Copdmentioning

confidence: 99%

“…62 Although little is known of the effects of PAF itself in the airways, the PAFR plays crucial roles in biological processes, including vasodilation, cell proliferation and angiogenesis, and in regulating inflammatory responses. 62 Notably, PAFR expression is increased in response to environmental exposures, in particular CS, air pollution, acids, viral infections, 60,63 welding fumes 64 and e-cigarette vapour. 65 Crucially, PAFR protein is increased in the large and small airways of COPD patients and correlates with current and previous smoking history.…”

Section: Role Of Pafr In Bacterial Persistencementioning

confidence: 99%

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Hypoxia‐inducible factor and bacterial infections in chronic obstructive pulmonary disease

et al. 2019

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COPD is a seriously disabling respiratory condition that inexorably progresses to disability and mortality. It affects approximately 10% of the population globally with a greater prevalence at advanced ages. Airway bacterial infections complicate the disease course in most COPD patients, leading to increased symptoms, more rapid decline in lung function, acute exacerbations and reduced quality of life. With increasing bacterial resistance to antibiotics and adverse effects of conventional treatments, new effective non‐antibiotic antimicrobial therapies are urgently needed to manage COPD. Hypoxia‐inducible factor (HIF)‐1α is an important transcriptional regulator of cellular responses to hypoxia, oxidants and inflammation, and is overexpressed in the lungs of COPD patients. Recent evidence shows that increased HIF‐1α expression can upregulate the platelet‐activating factor receptor (PAFR) on the airway epithelial surface that is increased in smokers and particularly COPD patients. The receptor is utilized by PAFR‐dependent bacteria (Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa) to induce infection in both the respiratory and gastrointestinal (GI) tracts. However, the importance and mechanism of HIF‐1α in augmenting PAFR‐dependent bacterial infections in COPD are poorly understood. Here, we review the evidence for the roles of local tissue hypoxia‐induced inflammation, HIF‐1α and PAFR in facilitating bacterial infections in COPD. Blocking PAFR may provide a novel antimicrobial approach to manage bacterial infections in COPD.

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Section: Hif-1α-induced Pafr-mediated Bacterial Infections In Copdmentioning

confidence: 91%

Section: Hif‐1α‐induced Pafr‐mediated Bacterial Infections In Copdmentioning

confidence: 99%

Section: Hif‐1α‐induced Pafr‐mediated Bacterial Infections In Copdmentioning

confidence: 99%

Section: Hif‐1α‐induced Pafr‐mediated Bacterial Infections In Copdmentioning

confidence: 99%

Section: Role Of Pafr In Bacterial Persistencementioning

confidence: 99%

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Hypoxia‐inducible factor and bacterial infections in chronic obstructive pulmonary disease

et al. 2019

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Pneumococcal vaccination for welders: Global deployment within a multi‐national corporation

Donoghue

Wesdock

2018

American J Industrial Med

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Background Lobar pneumonia is an occupational disease of welders. This is the first report of global deployment of a pneumococcal vaccination program for welders within a multi‐national corporation. Methods Global webinars were conducted to introduce the program. Communication packages translated into all location languages were deployed. All employee welders who had not previously been vaccinated were offered a free single dose of pneumococcal polysaccharide vaccine (PPV23) by on‐site location medical centers during normal working hours. Numbers of vaccinated welders were reported by each location each month. Results Twelve months after starting the program, 241 of 767 welders have been vaccinated (31%) across six countries. Conclusions Global deployment of pneumococcal vaccination for welders can be successfully undertaken by a multi‐national corporation. Adoption of this practice by corporations could reduce the incidence and mortality of pneumonia among welders globally.

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Mild steel welding is associated with alterations in circulating levels of cancer-related proteins

et al. 2019

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Welding fumes were recently classified as carcinogenic to humans and worldwide millions work as welders or perform welding operations. The purpose of this study was to identify new biomarkers of welding-induced carcinogenesis. We evaluated a panel of 91 putative cancer-related proteins in serum in a cohort of welders working with mild steel (n = 77) and controls (n = 94) from southern Sweden sampled on two occasions 6-year apart using a longitudinal analysis (linear mixed models). The significant results from the longitudinal analysis were tested for reproducibility in welders (n = 88) and controls (n = 69) sampled once during the same sampling period as timepoint 1 or timepoint 2 (linear regression models), i.e., in a cross-sectional setting. The models were adjusted for age, body-mass index, and use of snus. All study participants were non-smokers at recruitment. Exposure to welding fumes was assessed using questionnaires and respirable dust measurement in the breathing zone that was adjusted for personal respiratory protection equipment. The median respirable dust in welders was 0.7 (0.2-4.2) and 0.5 (0.1-1.9) mg/m 3 at the first and second timepoints, respectively. We identified 14 cancer-related proteins that were differentially expressed in welders versus controls in the longitudinal analysis, out of which three were also differentially expressed in the cross-sectional analysis (cross-sectional group). Namely, syndecan 1 (SDC1), folate receptor 1 (FOLR1), and secreted protein acidic and cysteine rich (SPARC) were downregulated, in welders compared with controls. In addition, FOLR1 was negatively associated with years welding. Disease and function analysis indicated that the top proteins are related to lung cancer as well as cell invasion and migration. Our study indicates that moderate exposure to welding fumes is associated with changes in circulating levels of putative cancer-related proteins, out of which FOLR1 showed a clear dose-response relationship. It is, however, unclear to which extent these changes are adaptive or potential early biomarkers of cancer.

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Pneumococcal infection of respiratory cells exposed to welding fumes; Role of oxidative stress and HIF-1 alpha

Cited by 21 publications

References 28 publications

Hypoxia‐inducible factor and bacterial infections in chronic obstructive pulmonary disease

Hypoxia‐inducible factor and bacterial infections in chronic obstructive pulmonary disease

Pneumococcal vaccination for welders: Global deployment within a multi‐national corporation

Mild steel welding is associated with alterations in circulating levels of cancer-related proteins

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