Premium
Swine Barn Dust Exposure Activates Microglia through Induction of Oxidative Stress and the Resultant Neuroinflammation Appears to Involve HMGB1 and RAGE Signaling
Author(s) -
Massey Nyzil,
Puttachary Sreekanth,
MahadevBhat Sanjana,
Shrestha Denusha,
Kanthasamy Anumantha G,
Charavaryamath Chandrashekhar
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.747.2
Subject(s) - microglia , neuroinflammation , rage (emotion) , hmgb1 , oxidative stress , inflammation , tlr4 , reactive oxygen species , downregulation and upregulation , chemistry , microbiology and biotechnology , immunology , biology , medicine , biochemistry , neuroscience , gene
Large swine farms employ full time workers who are exposed to occupational contaminants including organic dust, LPS, peptidoglycan and gases. Exposed workers mainly report bronchitis, asthma and loss of lung function. Most studies have focused on mechanisms of inflammation underlying respiratory symptoms. But effect of a continued exposure to swine barn dust on other vital organs such as brain have not been studied. Brain microglial cells are similar to macrophages of other organs in immune activation. Therefore, we tested a hypothesis that swine barn dust extract (SBDE) activates microglial cells of the brain. Settled dust from commercial swine operations was collected, buffer extract prepared and filter sterilized. Mouse microglial cell line (C57BL6) were treated with SBDE or lipolysachharide (LPS) or peptidoglycan (PGN) or medium and stained for the expression of, Iba1, gp91 phox (reactive oxygen species indicator), HMGB1 (high‐mobility group box‐1), RAGE (receptor for advanced glycation end products) and DAPI at 0, 6, 12, 24 and 48 h post treatment. Microglia morphologically appeared reactive with an upregulation gp91 phox by 24 hours post PGN or SBDE treatment. At 48 hours, SBDE treated microglia demonstrated translocation of nuclear HMGB1 into the cytoplasm. RAGE (transmembrane) was co‐localized with cytoplasmic HMGB1 in SBDE treated microglia. All these findings demonstrate that swine barn dust exposure can cause activation of microglia and induce oxidative stress. The resultant neuroinflammation appears to involve HMGB1 and RAGE signaling. Support or Funding Information Iowa State University, Ames, IA