{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T09:41:23Z","timestamp":1761990083862,"version":"build-2065373602"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T00:00:00Z","timestamp":1454544000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp; Exp Res"],"published-print":{"date-parts":[[2016,2]]},"abstract":"Background<\/jats:title>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 (TNF<\/jats:styled-content>\u2010\u03b1), interleukin\u20106 (IL<\/jats:styled-content>\u20106), and IL<\/jats:styled-content>\u20108. We have shown that alcohol alters airway epithelial innate defense through changes in both nitric oxide (NO<\/jats:styled-content>) and cAMP<\/jats:styled-content>\u2010dependent protein kinase A (PKA<\/jats:styled-content>). Simultaneous exposure to hog barn dust and alcohol decreases inflammatory mediators, TNF<\/jats:styled-content>\u2010\u03b1, IL<\/jats:styled-content>\u20106, and IL<\/jats:styled-content>\u20108, 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\u2010exposed to hog barn dust and alcohol also experienced increased mortality.<\/jats:p><\/jats:sec>Methods<\/jats:title>Because we recently demonstrated that PKA<\/jats:styled-content> activation inhibits the TNF<\/jats:styled-content>\u2010\u03b1 sheddase, TNF<\/jats:styled-content>\u2010\u03b1\u2010converting enzyme (TACE<\/jats:styled-content>), we hypothesized that an alcohol\u2010mediated PKA<\/jats:styled-content> pathway blocks TACE<\/jats:styled-content> activity and prevents the normative inflammatory response to hog barn dust exposure. To delineate these effects, we used PKA<\/jats:styled-content> pathway inhibitors (adenylyl cyclase [AC], cAMP<\/jats:styled-content>, and PKA<\/jats:styled-content>) to modulate the effects of alcohol on dust\u2010stimulated TNF<\/jats:styled-content>\u2010\u03b1 release in the bronchial epithelial cell line, BEAS<\/jats:styled-content>\u20102B. Alcohol pretreatment blocked TACE<\/jats:styled-content> activity and TNF<\/jats:styled-content>\u2010\u03b1 release in hog barn dust\u2010treated cells.<\/jats:p><\/jats:sec>Results<\/jats:title>Alcohol continued to block hog barn dust\u2010mediated TNF<\/jats:styled-content>\u2010\u03b1 release in the presence of the particulate AC inhibitor, SQ<\/jats:styled-content>22,536. The soluble adenylyl cyclase inhibitor, KH<\/jats:styled-content>7, however, significantly increased the inflammatory response to hog barn dust. phosphodiesterase 4 inhibitors significantly elevated cAMP<\/jats:styled-content> and enhanced alcohol\u2010mediated inhibition of dust\u2010stimulated TNF<\/jats:styled-content>\u2010\u03b1 release. In addition, the NO synthase inhibitor, l<\/jats:sc>\u2010NMMA<\/jats:styled-content>, also reversed the alcohol\u2010blocking effect on dust\u2010stimulated TNF<\/jats:styled-content>\u2010\u03b1.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>These data suggest that alcohol requires a soluble cyclase\u2010generated cAMP<\/jats:styled-content>\u2010PKA<\/jats:styled-content> pathway that is dependent upon the action of NO<\/jats:styled-content> to inhibit TACE<\/jats:styled-content> and TNF<\/jats:styled-content>\u2010\u03b1 release. These findings support our observations that alcohol functions through a dual NO<\/jats:styled-content> and PKA<\/jats:styled-content> pathway in bronchial epithelial cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.12967","type":"journal-article","created":{"date-parts":[[2016,2,8]],"date-time":"2016-02-08T02:02:14Z","timestamp":1454896934000},"page":"273-283","source":"Crossref","is-referenced-by-count":6,"title":["Alcohol Decreases Organic Dust\u2010Stimulated Airway Epithelial TNF<\/scp>\u2010Alpha Through a Nitric Oxide and Protein Kinase\u2010Mediated Inhibition of TACE<\/scp>"],"prefix":"10.1111","volume":"40","author":[{"given":"Carresse L.","family":"Gerald","sequence":"first","affiliation":[{"name":"Pulmonary, Critical Care, Sleep & Allergy Division Department of Internal Medicine Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra J.","family":"Romberger","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care, Sleep & Allergy Division Department of Internal Medicine Nebraska Medical Center Omaha Nebraska"},{"name":"Department of Veterans Affairs Medical Center VA Nebraska\u2010Western Iowa Health Care System Research Service Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane M.","family":"DeVasure","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care, Sleep & Allergy Division Department of Internal Medicine Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohan","family":"Khazanchi","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care, Sleep & Allergy Division Department of Internal Medicine Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara M.","family":"Nordgren","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care, Sleep & Allergy Division Department of Internal Medicine Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Art J.","family":"Heires","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care, Sleep & Allergy Division Department of Internal Medicine Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph H.","family":"Sisson","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care, Sleep & Allergy Division Department of Internal Medicine Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd A.","family":"Wyatt","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care, Sleep & Allergy Division Department of Internal Medicine Nebraska Medical Center Omaha Nebraska"},{"name":"Department of Veterans Affairs Medical Center VA Nebraska\u2010Western Iowa Health Care System Research Service Omaha Nebraska"},{"name":"Department of Environmental, Agricultural, and Occupational Health College of Public Health University of Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,2,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2007.11.014"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000095634.82310.53"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095578"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2004.08.002"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00346.2006"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jrh.12001"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.2000.15.22.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.6.2695"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0178OC"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2005-0440OC"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2003.06.005"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.3844\/ajabssp.2014.153.166"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200507-065JS"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2006.00144.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1396"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01602.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)91285-5"},{"key":"e_1_2_6_19_1","unstructured":"KandelW(2008)Profile of Hired Farmworkers A 2008 Update. 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