Immune Modulation as an Effective Adjunct Post-exposure Therapeutic for B. pseudomallei.
Melioidosis is caused by the facultative intracellular bacterium Burkholderia pseudomallei and is potentially fatal. Despite a growing global burden and high fatality rate, little is known about the disease. Recent studies demonstrate that cyclooxygenase-2 (COX-2) inhibition is an effective post-exp...
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ftdoajarticles:oai:doaj.org/article:66edc4060af546d18cef03821edc386c 2023-05-15T15:16:44+02:00 Immune Modulation as an Effective Adjunct Post-exposure Therapeutic for B. pseudomallei. William J Wilson Maryam F Afzali Jason E Cummings Marie E Legare Ronald B Tjalkens Christopher P Allen Richard A Slayden William H Hanneman 2016-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005065 https://doaj.org/article/66edc4060af546d18cef03821edc386c EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5085046?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005065 https://doaj.org/article/66edc4060af546d18cef03821edc386c PLoS Neglected Tropical Diseases, Vol 10, Iss 10, p e0005065 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005065 2022-12-31T16:22:43Z Melioidosis is caused by the facultative intracellular bacterium Burkholderia pseudomallei and is potentially fatal. Despite a growing global burden and high fatality rate, little is known about the disease. Recent studies demonstrate that cyclooxygenase-2 (COX-2) inhibition is an effective post-exposure therapeutic for pulmonary melioidosis, which works by inhibiting the production of prostaglandin E2 (PGE2). This treatment, while effective, was conducted using an experimental COX-2 inhibitor that is not approved for human or animal use. Therefore, an alternative COX-2 inhibitor needs to be identified for further studies. Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug (NSAID) COX-2 inhibitor marketed outside of the United States for the treatment of migraines. While this drug was developed for COX-2 inhibition, it has been found to modulate other aspects of inflammation as well. In this study, we used RAW 264.7 cells infected with B pseudomallei to analyze the effect of TA on cell survival, PGE2 production and regulation of COX-2 and nuclear factor- kappaB (NF-ĸB) protein expression. To evaluate the effectiveness of post-exposure treatment with TA, results were compared to Ceftazidime (CZ) treatments alone and the co-treatment of TA with a sub-therapeutic treatment of CZ determined in a study of BALB/c mice. Results revealed an increase in cell viability in vitro with TA and were able to reduce both COX-2 expression and PGE2 production while also decreasing NF-ĸB activation during infection. Co-treatment of orally administered TA and a sub-therapeutic treatment of CZ significantly increased survival outcome and cleared the bacterial load within organ tissue. Additionally, we demonstrated that post-exposure TA treatment with sub-therapeutic CZ is effective to treat melioidosis in BALB/c mice. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 10 e0005065 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 William J Wilson Maryam F Afzali Jason E Cummings Marie E Legare Ronald B Tjalkens Christopher P Allen Richard A Slayden William H Hanneman Immune Modulation as an Effective Adjunct Post-exposure Therapeutic for B. pseudomallei. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Melioidosis is caused by the facultative intracellular bacterium Burkholderia pseudomallei and is potentially fatal. Despite a growing global burden and high fatality rate, little is known about the disease. Recent studies demonstrate that cyclooxygenase-2 (COX-2) inhibition is an effective post-exposure therapeutic for pulmonary melioidosis, which works by inhibiting the production of prostaglandin E2 (PGE2). This treatment, while effective, was conducted using an experimental COX-2 inhibitor that is not approved for human or animal use. Therefore, an alternative COX-2 inhibitor needs to be identified for further studies. Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug (NSAID) COX-2 inhibitor marketed outside of the United States for the treatment of migraines. While this drug was developed for COX-2 inhibition, it has been found to modulate other aspects of inflammation as well. In this study, we used RAW 264.7 cells infected with B pseudomallei to analyze the effect of TA on cell survival, PGE2 production and regulation of COX-2 and nuclear factor- kappaB (NF-ĸB) protein expression. To evaluate the effectiveness of post-exposure treatment with TA, results were compared to Ceftazidime (CZ) treatments alone and the co-treatment of TA with a sub-therapeutic treatment of CZ determined in a study of BALB/c mice. Results revealed an increase in cell viability in vitro with TA and were able to reduce both COX-2 expression and PGE2 production while also decreasing NF-ĸB activation during infection. Co-treatment of orally administered TA and a sub-therapeutic treatment of CZ significantly increased survival outcome and cleared the bacterial load within organ tissue. Additionally, we demonstrated that post-exposure TA treatment with sub-therapeutic CZ is effective to treat melioidosis in BALB/c mice. |
format |
Article in Journal/Newspaper |
author |
William J Wilson Maryam F Afzali Jason E Cummings Marie E Legare Ronald B Tjalkens Christopher P Allen Richard A Slayden William H Hanneman |
author_facet |
William J Wilson Maryam F Afzali Jason E Cummings Marie E Legare Ronald B Tjalkens Christopher P Allen Richard A Slayden William H Hanneman |
author_sort |
William J Wilson |
title |
Immune Modulation as an Effective Adjunct Post-exposure Therapeutic for B. pseudomallei. |
title_short |
Immune Modulation as an Effective Adjunct Post-exposure Therapeutic for B. pseudomallei. |
title_full |
Immune Modulation as an Effective Adjunct Post-exposure Therapeutic for B. pseudomallei. |
title_fullStr |
Immune Modulation as an Effective Adjunct Post-exposure Therapeutic for B. pseudomallei. |
title_full_unstemmed |
Immune Modulation as an Effective Adjunct Post-exposure Therapeutic for B. pseudomallei. |
title_sort |
immune modulation as an effective adjunct post-exposure therapeutic for b. pseudomallei. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0005065 https://doaj.org/article/66edc4060af546d18cef03821edc386c |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 10, p e0005065 (2016) |
op_relation |
http://europepmc.org/articles/PMC5085046?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005065 https://doaj.org/article/66edc4060af546d18cef03821edc386c |
op_doi |
https://doi.org/10.1371/journal.pntd.0005065 |
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PLOS Neglected Tropical Diseases |
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10 |
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10 |
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e0005065 |
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