Pattern recognition scavenger receptor A/CD204 regulates airway inflammatory homeostasis following organic dust extract exposures

Poole, Jill; Anderson, Leigh C.; Gleason, Angela M.; West, William W.; Romberger, Debra J.; Wyatt, Todd A.

doi:10.3109/1547691x.2014.882449

Cited by 21 publications

(29 citation statements)

References 35 publications

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“…In the present study, we investigated whether high dietary supplementation with vitamin D would reduce airway inflammatory responses following three weeks of daily, repetitive inhalant exposure to ODE or LPS. Consistent with previous work [10, 21], repetitive ODE treatment resulted in significant increases in total cell influx including neutrophils, macrophages, and lymphocytes (Figure 1). Repetitive treatment with LPS also resulted in significant increases in total cell influx including neutrophils, and lymphocytes as compared to saline, but to a significantly lesser magnitude as compared to ODE treatment (Figure 1).…”

Section: Resultssupporting

confidence: 92%

“…Aqueous ODE was collected and prepared as previously described [11, 21]. Briefly, settled surface dust samples (~3 feet off ground) from swine confinement animal feeding operations (~500–700 animals) were collected and 1 gm was placed into sterile Hank’s Balanced Salt Solution (10 ml; Sigma, St. Louis, MO), incubated for one hour at room temperature, and centrifuged for 20 minutes at 2000 x g .…”

Section: Methodsmentioning

confidence: 99%

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Vitamin D supplementation protects against bone loss following inhalant organic dust and lipopolysaccharide exposures in mice

et al. 2015

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Systemic bone loss is associated with airway inflammatory diseases; yet, strategies to halt disease progression from inhalant exposures are not clear. Vitamin D might be a potentially protective approach against noxious respirable environmental exposures. We sought to determine whether vitamin D supplementation represents a viable lung and bone protective strategy following repetitive inhalant treatments with organic dust extract (ODE) or lipopolysaccharide (LPS) in mice. C57BL/5 mice were maintained on diets with low (1 IU/D/g) or high (10 IU/D/g) vitamin D for 5 weeks, and treated with ODE from swine confinement facilities, LPS, or saline daily for 3 weeks per established intranasal inhalation protocol. Lungs, hind limbs, and sera were harvested for experimental outcomes. Serum 25-hydroxy vitamin D levels were 10-fold different between low/high vitamin D treatment groups with no differences between inhalant agents/saline treatments. Serum calcium levels were not affected. There was no difference in the magnitude of ODE- or LPS-induced inflammatory cell influx or lung histopathology between high/low vitamin D treatment groups. However, high vitamin D treatment reversed the loss of bone mineral density, bone volume, and bone microarchitecture deterioration induced by ODE or LPS as determined by micro-CT analysis. Bone-resorbing osteoclasts were also reduced by high vitamin D treatment. In the low vitamin D treatment groups, ODE induced the greatest degree of airway inflammatory consequences, and LPS induced the greatest degree of bone loss. Collectively, high concentration vitamin D was protective against systemic bone loss, but not airway inflammation, resulting from ODE- or LPS-induced airway injury.

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Section: Resultssupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Vitamin D supplementation protects against bone loss following inhalant organic dust and lipopolysaccharide exposures in mice

et al. 2015

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“…It was also shown that the adaptor protein myeloid differentiation factor 88 (MyD88), which is utilized by all TLRs (except TLR3) and IL-1R/IL18R, plays a central role, because mice deficient in MyD88 were nearly completely protected against swine facility dust extract-induced acute airway inflammatory responses (35). Scavenger receptors might also represent an important pathway as researchers reported that scavenger receptor A (CD204) deficient mice had increased airway inflammatory consequences to organic dust extract treatment (37). Next, a study of swine confinement workers in Canada found that polymorphisms of the TLR2 gene were associated with improved lung function; polymorphisms in the TLR4 gene were not associated with lung function changes (38).…”

Section: Resultsmentioning

confidence: 99%

Occupational agriculture organic dust exposure and its relationship to asthma and airway inflammation in adults

Wunschel

Poole²

2016

Journal of Asthma

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Objective Recent studies have made advances into understanding the complex agriculture work exposure environment in influencing asthma in adults. The objective of this study is to review studies of occupational agricultural exposures including dust, animal, and pesticide exposures with asthma in adult populations. Data Sources PubMed databases were searched for articles pertaining to farming, agriculture, asthma, occupational asthma, airway inflammation, respiratory disease, lung disease, pesticides and organic dust. Study Selections Studies chosen were published in or after 1999 that included adults and asthma and farming/agricultural work or agricultural exposures and airway inflammatory disease measurements. Results The data remains inconclusive. Several retrospective studies demonstrate agricultural work to be protective against asthma in adults, especially with increased farming exposure over time. In contrast, other studies find increased risk of asthma with farming exposures, especially for the non-atopic adult. Mechanistic and genetic studies have focused on defining the wide variety and abundance of microorganisms within these complex organic dusts that trigger several pattern recognition receptor pathways to modulate the hosts’ response. Conclusion Asthma risk depends on the interplay of genetic factors, gender, atopic predisposition, type of livestock, pesticide exposure, and magnitude and duration of exposure in the adult subject. Longer exposure to occupational farming is associated with decreased asthma risk. However, studies also suggest that agricultural work and multiple types of livestock are independent risk factors for developing asthma. Prospective and longitudinal studies focusing on genetic polymorphisms, objective assessments, and environmental sampling are needed to further delineate the influence of agriculture exposure in the adult worker.

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“…Dust was collected from raised surfaces of hog confinement facilities and an aqueous extract prepared as previously detailed (Dusad et al, 2013; Poole et al, 2014). The dust was made into an aqueous extract (HDE; hog barn dust extract) by vortexing 1g/ml of dust into Hank’s balanced salt solutions (HBSS) for 1 min and allowed to sit for 1 hr.…”

Section: Methodsmentioning

confidence: 99%

Alcohol Decreases Organic Dust‐Stimulated Airway Epithelial TNF‐Alpha Through a Nitric Oxide and Protein Kinase‐Mediated Inhibition of TACE

Gerald

Romberger

DeVasure

et al. 2016

Alcoholism Clin & Exp Res

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Background Farm workers in rural areas consume more alcohol than those who reside in urban areas. Occupational exposures such as agricultural work can pose hazards on the respiratory system. It is established that hog barn dust induces inflammation in the airway, including the release of cytokines such as tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6) and interleukin-8 (IL-8). We have shown that alcohol alters airway epithelial innate defense through changes in both nitric oxide (NO) and cAMP-dependent protein kinase (PKA). Simultaneous exposure to hog barn dust and alcohol decreases inflammatory mediators, TNFα, IL-6 and IL-8, in mice. Previously, mice exposed to both alcohol and hog barn dust showed a depleted amount of lymphocytes compared to mice exposed only to hog barn dust. Weakening of the innate immune response could lead to enhanced susceptibility to disease. In addition, mice that were co-exposed to hog barn dust and alcohol also experienced increased mortality. Methods Because we recently demonstrated that PKA activation inhibits the TNFα sheddase, TNF-α converting enzyme (TACE), we hypothesized that an alcohol-mediated PKA pathway blocks TACE activity and prevents the normative inflammatory response to hog barn dust exposure. To delineate these effects, we used PKA pathway inhibitors (adenylyl cyclase, cAMP and PKA) to modulate the effects of alcohol on dust-stimulated TNFα release in the bronchial epithelial cell line, BEAS-2B. Alcohol pretreatment blocked TACE activity and TNFα release in hog barn dust-treated cells. Results Alcohol continued to block hog barn dust-mediated TNFα release in the presence of the particulate adenylyl cyclase inhibitor, SQ22,536. The soluble adenylyl cyclase (sAC) inhibitor, KH7, however, significantly increased the inflammatory response to hog barn dust. PDE4 inhibitors significantly elevated cAMP and enhanced alcohol-mediated inhibition of dust-stimulated TNFα release. In addition, the nitric oxide synthase inhibitor, L-NMMA, also reversed the alcohol-blocking effect on dust-stimulated TNFα. Conclusions These data suggest that alcohol requires a soluble cyclase-generated cAMP-PKA pathway that is dependent upon the action of NO to inhibit TACE and TNFα release. These findings support our observations that alcohol functions through a dual NO and PKA pathway in bronchial epithelial cells.

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Pattern recognition scavenger receptor A/CD204 regulates airway inflammatory homeostasis following organic dust extract exposures

Cited by 21 publications

References 35 publications

Vitamin D supplementation protects against bone loss following inhalant organic dust and lipopolysaccharide exposures in mice

Vitamin D supplementation protects against bone loss following inhalant organic dust and lipopolysaccharide exposures in mice

Occupational agriculture organic dust exposure and its relationship to asthma and airway inflammation in adults

Alcohol Decreases Organic Dust‐Stimulated Airway Epithelial TNF‐Alpha Through a Nitric Oxide and Protein Kinase‐Mediated Inhibition of TACE

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