Ethyl pyruvate reduces organic dust-induced airway inflammation by targeting HMGB1-RAGE signaling
Abstract Background Animal production workers are persistently exposed to organic dust and can suffer from a variety of respiratory disease symptoms and annual decline in lung function. The role of high mobility group box-1 (HMGB1) in inflammatory airway diseases is emerging. Hence, we tested a hypo...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12931-019-0992-3 |
| _version_ | 1818019830716956672 |
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| author | Sanjana Mahadev Bhat Nyzil Massey Locke A. Karriker Baljit Singh Chandrashekhar Charavaryamath |
| author_facet | Sanjana Mahadev Bhat Nyzil Massey Locke A. Karriker Baljit Singh Chandrashekhar Charavaryamath |
| author_sort | Sanjana Mahadev Bhat |
| collection | DOAJ |
| description | Abstract Background Animal production workers are persistently exposed to organic dust and can suffer from a variety of respiratory disease symptoms and annual decline in lung function. The role of high mobility group box-1 (HMGB1) in inflammatory airway diseases is emerging. Hence, we tested a hypothesis that organic dust exposure of airway epithelial cells induces nucleocytoplasmic translocation of HMGB1 and blocking this translocation dampens organic dust-induced lung inflammation. Methods Rats were exposed to either ambient air or swine barn (8 h/day for either 1, 5, or 20 days) and lung tissues were processed for immunohistochemistry. Swine barn dust was collected and organic dust extract (ODE) was prepared and sterilized. Human airway epithelial cell line (BEAS-2B) was exposed to either media or organic dust extract followed by treatment with media or ethyl pyruvate (EP) or anti-HMGB1 antibody. Immunoblotting, ELISA and other assays were performed at 0 (control), 6, 24 and 48 h. Data (as mean ± SEM) was analyzed using one or two-way ANOVA followed by Bonferroni’s post hoc comparison test. A p value of less than 0.05 was considered significant. Results Compared to controls, barn exposed rats showed an increase in the expression of HMGB1 in the lungs. Compared to controls, ODE exposed BEAS-2B cells showed nucleocytoplasmic translocation of HMGB1, co-localization of HMGB1 and RAGE, reactive species and pro-inflammatory cytokine production. EP treatment reduced the ODE induced nucleocytoplasmic translocation of HMGB1, HMGB1 expression in the cytoplasmic fraction, GM-CSF and IL-1β production and augmented the production of TGF-β1 and IL-10. Anti-HMGB1 treatment reduced ODE-induced NF-κB p65 expression, IL-6, ROS and RNS but augmented TGF-β1 and IL-10 levels. Conclusions HMGB1-RAGE signaling is an attractive target to abrogate OD-induced lung inflammation. |
| first_indexed | 2024-04-14T07:56:45Z |
| format | Article |
| id | doaj.art-6fbc1ac81e164432972d2f7e02ff3d01 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-14T07:56:45Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-6fbc1ac81e164432972d2f7e02ff3d012022-12-22T02:05:01ZengBMCRespiratory Research1465-993X2019-02-0120111910.1186/s12931-019-0992-3Ethyl pyruvate reduces organic dust-induced airway inflammation by targeting HMGB1-RAGE signalingSanjana Mahadev Bhat0Nyzil Massey1Locke A. Karriker2Baljit Singh3Chandrashekhar Charavaryamath4Department of Biomedical Sciences, 2008 Vet Med Building, Iowa State UniversityDepartment of Biomedical Sciences, 2008 Vet Med Building, Iowa State UniversityDepartment of Veterinary Diagnostic and Production Animal Medicine, 2203 Lloyd Veterinary Medical Center, Iowa State universityFaculty of Veterinary Medicine, 2500 University Dr. NW, University of CalgaryDepartment of Biomedical Sciences, 2008 Vet Med Building, Iowa State UniversityAbstract Background Animal production workers are persistently exposed to organic dust and can suffer from a variety of respiratory disease symptoms and annual decline in lung function. The role of high mobility group box-1 (HMGB1) in inflammatory airway diseases is emerging. Hence, we tested a hypothesis that organic dust exposure of airway epithelial cells induces nucleocytoplasmic translocation of HMGB1 and blocking this translocation dampens organic dust-induced lung inflammation. Methods Rats were exposed to either ambient air or swine barn (8 h/day for either 1, 5, or 20 days) and lung tissues were processed for immunohistochemistry. Swine barn dust was collected and organic dust extract (ODE) was prepared and sterilized. Human airway epithelial cell line (BEAS-2B) was exposed to either media or organic dust extract followed by treatment with media or ethyl pyruvate (EP) or anti-HMGB1 antibody. Immunoblotting, ELISA and other assays were performed at 0 (control), 6, 24 and 48 h. Data (as mean ± SEM) was analyzed using one or two-way ANOVA followed by Bonferroni’s post hoc comparison test. A p value of less than 0.05 was considered significant. Results Compared to controls, barn exposed rats showed an increase in the expression of HMGB1 in the lungs. Compared to controls, ODE exposed BEAS-2B cells showed nucleocytoplasmic translocation of HMGB1, co-localization of HMGB1 and RAGE, reactive species and pro-inflammatory cytokine production. EP treatment reduced the ODE induced nucleocytoplasmic translocation of HMGB1, HMGB1 expression in the cytoplasmic fraction, GM-CSF and IL-1β production and augmented the production of TGF-β1 and IL-10. Anti-HMGB1 treatment reduced ODE-induced NF-κB p65 expression, IL-6, ROS and RNS but augmented TGF-β1 and IL-10 levels. Conclusions HMGB1-RAGE signaling is an attractive target to abrogate OD-induced lung inflammation.http://link.springer.com/article/10.1186/s12931-019-0992-3Organic dustHMGB1RAGELung inflammationEthyl pyruvate |
| spellingShingle | Sanjana Mahadev Bhat Nyzil Massey Locke A. Karriker Baljit Singh Chandrashekhar Charavaryamath Ethyl pyruvate reduces organic dust-induced airway inflammation by targeting HMGB1-RAGE signaling Respiratory Research Organic dust HMGB1 RAGE Lung inflammation Ethyl pyruvate |
| title | Ethyl pyruvate reduces organic dust-induced airway inflammation by targeting HMGB1-RAGE signaling |
| title_full | Ethyl pyruvate reduces organic dust-induced airway inflammation by targeting HMGB1-RAGE signaling |
| title_fullStr | Ethyl pyruvate reduces organic dust-induced airway inflammation by targeting HMGB1-RAGE signaling |
| title_full_unstemmed | Ethyl pyruvate reduces organic dust-induced airway inflammation by targeting HMGB1-RAGE signaling |
| title_short | Ethyl pyruvate reduces organic dust-induced airway inflammation by targeting HMGB1-RAGE signaling |
| title_sort | ethyl pyruvate reduces organic dust induced airway inflammation by targeting hmgb1 rage signaling |
| topic | Organic dust HMGB1 RAGE Lung inflammation Ethyl pyruvate |
| url | http://link.springer.com/article/10.1186/s12931-019-0992-3 |
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