Selenium attenuates pro-inflammatory gene expression in macrophages.
Selenium (Se) is an important element required for the optimal functioning of the immune system. Particularly in macrophages, which play a pivotal role in immune regulation, Se acts as a major antioxidant in the form of selenoproteins to mitigate the cytotoxic effects of reactive oxygen species. Here we describe the role of Se as an anti-inflammatory agent and its effect on the macrophage signal transduction pathways elicited by bacterial endotoxin, LPS. Our studies demonstrate that supplementation of Se to macrophages (Se-deficient) leads to a significant decrease in the LPS-induced expression of two important pro-inflammatory genes, cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-alpha) via the inhibition of MAP kinase pathways. Furthermore, Se-deficiency in mice exacerbated the LPS-mediated infiltration of macrophages into the lungs suggesting that Se status is a crucial host factor that regulates inflammation. In summary, our results indicate that Se plays an important role as an anti-inflammatory agent by tightly regulating the expression of pro-inflammatory genes in immune cells.
Vunta
Hema
H
Department of Veterinary and Biomedical Sciences, Center for Molecular Toxicology and Carcinogenesis and Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, PA 16801, USA.
Belda
Benjamin J
BJ
Arner
Ryan J
RJ
Channa Reddy
C
C
Vanden Heuvel
John P
JP
Sandeep Prabhu
K
K
D000818:Animals; D002460:Cell Line; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000235:genetics; D007249:Inflammation / Q000235:genetics* / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012643:Selenium / Q000172:deficiency / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse