Arsenic upregulates MMP-9 and inhibits wound repair in human airway epithelial cells

Olsen, Colin E.; Liguori, Andrew E.; Zong, Yue; Lantz, R. Clark; Burgess, Jefferey L.; Boitano, Scott

doi:10.1152/ajplung.00134.2007

Cited by 53 publications

(61 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animal studies showed tissue inflammation and increased morphologic changes in the lung with increasing arsenic exposure (31,35). Impaired repair mechanisms in the human epithelium of the airway have also been demonstrated by the up-regulation of metalloproteinase-9 in extracellular matrix in arsenic-exposed subjects (36). Clara cell 16 protein, which is known to play an important role in protecting the alveolar epithelium of the lung in chronic inflammation (37,38), has also been impacted by arsenic exposure (27).…”

Section: Discussionmentioning

confidence: 99%

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

Parvez

Chen

Yunus

et al. 2013

Am J Respir Crit Care Med

112

View full text Add to dashboard Cite

Rationale: Exposure to arsenic through drinking water has been linked to respiratory symptoms, obstructive lung diseases, and mortality from respiratory diseases. Limited evidence for the deleterious effects on lung function exists among individuals exposed to a high dose of arsenic. Objectives: To determine the deleterious effects on lung function that exist among individuals exposed to a high dose of arsenic. Methods: In 950 individuals who presented with any respiratory symptom among a population-based cohort of 20,033 adults, we evaluated the association between arsenic exposure, measured by well water and urinary arsenic concentrations measured at baseline, and post-bronchodilator-administered pulmonary function assessed during follow-up. Measurements and Main Results: For every one SD increase in baseline water arsenic exposure, we observed a lower level of FEV 1 (246.5 ml; P , 0.0005) and FVC (253.1 ml; P , 0.01) in regression models adjusted for age, sex, body mass index, smoking, socioeconomic status, betel nut use, and arsenical skin lesions status. Similar inverse relationships were observed between baseline urinary arsenic and FEV 1 (248.3 ml; P , 0.005) and FVC (255.2 ml; P , 0.01) in adjusted models. Our analyses also demonstrated a dose-related decrease in lung function with increasing levels of baseline water and urinary arsenic. This association remained significant in never-smokers and individuals without skin lesions, and was stronger in male smokers. Among male smokers and individuals with skin lesions, every one SD increase in water arsenic was related to a significant reduction of FEV 1 (274.4 ml, P , 0.01; and 2116.1 ml, P , 0.05) and FVC (272.8 ml, P ¼ 0.02; and 2146.9 ml, P ¼ 0.004), respectively. Conclusions: This large population-based study confirms that arsenic exposure is associated with impaired lung function and the deleterious effect is evident at low-to moderate-dose range.Keywords: arsenic exposure; lung function; Bangladesh Arsenic from drinking water has been linked with cancers, dermatologic, cardiovascular, reproductive, and neurotoxic outcomes among adults and children (1-8). Chronic exposure to arsenic has also been linked to nonmalignant respiratory effects including respiratory symptoms, chronic obstructive pulmonary disease, and respiratory disease mortality (9-12). However, the evidence of the effect of arsenic exposure on lung function is limited, especially at the low-to moderate-dose ranges. Several studies from arsenic-endemic areas of South Asia reported lower FEV 1 and FVC among individuals with arsenical skin lesions or drinking water with very high levels of arsenic (.250 mg/L) (13-15). Interestingly, a recent retrospective study from Chile identified that those exposed to arsenic either in utero or early life had a lower FEV 1 (11.5%; P ¼ 0.04) and FVC (12.2%; P ¼ 0.04) in adulthood compared with those unexposed (16).The published studies measuring pulmonary function involved small sample sizes and most lacked individual-level exposure data or measured arseni...

show abstract

Section: Discussionmentioning

confidence: 99%

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

Parvez

Chen

Yunus

et al. 2013

Am J Respir Crit Care Med

112

View full text Add to dashboard Cite

show abstract

“…MMP-9 has also been shown to stimulate the repair of bronchial epithelial cells in vitro (94), and MMP-9-mediated stimulation of HBE cell migration was shown to be dependent on the activation of dual oxidase 1 (Duox1) (184). In contrast, exposure of 16HBE14o-to arsenic caused increased MMP-9 activity and expression and decreased cell migration, whereas inhibition of MMP-9 enhanced wound repair (113). Another group previously found that plasminogen activator inhibitor-1 (PAI-1), another protein associated with matrix degradation, decreased the repair of ATII cells by binding to vitronectin (89).…”

Section: Matrix Integrins and Glycoproteinsmentioning

confidence: 99%

Epithelial repair mechanisms in the lung

Crosby

Waters

2010

American Journal of Physiology-Lung Cellular and Molecular Phys

614

552

View full text Add to dashboard Cite

The recovery of an intact epithelium following lung injury is critical for restoration of lung homeostasis. The initial processes following injury include an acute inflammatory response, recruitment of immune cells, and epithelial cell spreading and migration upon an autologously secreted provisional matrix. Injury causes the release of factors that contribute to repair mechanisms including members of the epidermal growth factor and fibroblast growth factor families (TGF-alpha, KGF, HGF), chemokines (MCP-1), interleukins (IL-1beta, IL-2, IL-4, IL-13), and prostaglandins (PGE(2)), for example. These factors coordinate processes involving integrins, matrix materials (fibronectin, collagen, laminin), matrix metalloproteinases (MMP-1, MMP-7, MMP-9), focal adhesions, and cytoskeletal structures to promote cell spreading and migration. Several key signaling pathways are important in regulating these processes, including sonic hedgehog, Rho GTPases, MAP kinase pathways, STAT3, and Wnt. Changes in mechanical forces may also affect these pathways. Both localized and distal progenitor stem cells are recruited into the injured area, and proliferation and phenotypic differentiation of these cells leads to recovery of epithelial function. Persistent injury may contribute to the pathology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. For example, dysregulated repair processes involving TGF-beta and epithelial-mesenchymal transition may lead to fibrosis. This review focuses on the processes of epithelial restitution, the localization and role of epithelial progenitor stem cells, the initiating factors involved in repair, and the signaling pathways involved in these processes.

show abstract

“…This chapter specifically addresses the mechanisms implicated in the carcinogenic and neurotoxic effects of arsenic. Further effects such as those on cutaneous and systemic immunity (Biswas et al, 2008;Olsen et al, 2008;Liao et al, 2009b;Raqib et al, 2009), on developmental and reproductive toxicity and on endocrine processes including estrogen receptor mediated signalling (Watson and Yager, 2007) are partly addressed in the respective sections but are not addressed in detail here.…”

Section: Molecular Mechanismsmentioning

confidence: 99%

Scientific Opinion on Arsenic in Food

2009

EFSA Journal

877

220

View full text Add to dashboard Cite

The EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) assessed the risks to human health related to the presence of arsenic in food. More than 100,000 occurrence data on arsenic in food were considered with approximately 98 % reported as total arsenic. Making a number of assumptions for the contribution of inorganic arsenic to total arsenic, the inorganic arsenic exposure from food and water across 19 European countries, using lower bound and upper bound concentrations, has been estimated to range from 0.13 to 0.56 µg/kg bodyweight (b.w.) per day for average consumers, and from 0.37 to 1.22 µg/kg b.w. per day for 95 th percentile consumers. Dietary exposure to inorganic arsenic for children under three years of age is in general estimated to be from 2 to 3-fold that of adults. The CONTAM Panel concluded that the provisional tolerable weekly intake (PTWI) of 15 µg/kg b.w. established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) is no longer appropriate as data had shown that inorganic arsenic causes cancer of the lung and urinary bladder in addition to skin, and that a range of adverse effects had been reported at exposures lower than those reviewed by the JECFA. The CONTAM Panel modelled the dose-response data from key for providing consumption information and calculating exposure, the partners of the EFSA project on the "Individual food consumption data and exposure" coordinated by Ghent University (Department of Public Health, University Hospital, Ghent University, Belgium), and RIKILT (Institute of Food Safety, Wageningen, The Netherlands) for the accessibility of the exposure assessment tools. 4 Table of contents shows now the fourth level of subheadings. 5 An error in the interpretation of the total number of the population in the study of Rahman et al. (2006a) was discovered (Table 41). The BMDL was recalculated and as a consequence it was not considered a potential reference point. The text in the opinion, Table 43 and Appendix were revised accordingly. In addition, the header of the "total number of cases" was replaced by "total number of individuals" in Tables 40-42 and the erroneous units were corrected to µg/L in the text below SUMMARYArsenic is a metalloid that occurs in different inorganic and organic forms, which are found in the environment both from natural occurrence and from anthropogenic activity. The inorganic forms of arsenic are more toxic as compared to the organic arsenic but so far most of the occurrence data in food collected in the framework of official food control are still reported as total arsenic without differentiating the various arsenic species. The need for speciation data is evident because several investigations have shown that especially in seafood most of the arsenic is present in organic forms that are less toxic. Consequently, a risk assessment not taking into account the different species but considering total arsenic as being present exclusively as inorganic arsenic would lead to a considerable overestimation of the health risk rel...

show abstract

Arsenic upregulates MMP-9 and inhibits wound repair in human airway epithelial cells

Cited by 53 publications

References 50 publications

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

Epithelial repair mechanisms in the lung

Scientific Opinion on Arsenic in Food

Contact Info

Product

Resources

About