Heme oxygenase-1 mediates cytoprotective effects of immunostimulation in microglia.
Microglia are brain-resident immune cells playing a pivotal role in the neuroinflammation. Previously, it has been shown that immunostimulation protects microglial cells against nitric oxide toxicity. Herein, we report that heme oxygenase-1 (HO-1) mediates the protective effects of immunostimulation. Pro-inflammatory activation of BV-2 microglial cells with endotoxin lipopolysaccharide (LPS) conferred a protection against various cytotoxic stimuli, whereas anti-inflammatory cytokines such as IL-4 and IL-10 were without effects. The LPS-induced cytoprotection was accompanied by HO-1 induction. The cytoprotective effect of LPS treatment was significantly attenuated by co-treatment with a HO-1 inhibitor, zinc protoporphyrin. Adenoviral expression of HO-1 in microglial cells was similarly cytoprotective, indicating that HO-1 mediates the cytoprotective effects of pro-inflammatory stimulation. Additional experiments revealed the involvement of carbon monoxide (CO) and iron, products of HO-1-mediated heme degradation, in the cytoprotective effect of LPS. Taken together, our results suggest that immunostimulation of microglia with LPS provides cytoprotective effects via HO-1 induction followed by the generation of CO and iron.
Lee
Shinrye
S
Department of Pharmacology, Kyungpook National University School of Medicine, 101 Dong-In, Joong-gu, Daegu 700-422, Republic of Korea.
Suk
Kyoungho
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002248:Carbon Monoxide / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D002248:Carbon Monoxide; D007501:Iron; D051547:Heme Oxygenase-1