Hydroquinone, a reactive metabolite of benzene, reduces macrophage-mediated immune responses.
Hydroquinone is a toxic compound and a major benzene metabolite. We report that it strongly inhibits the activation of macrophages and associated cells. Thus, it suppressed the production of proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-3, IL-6, IL-10, IL-12p40, IL-23], secretion of toxic molecules [nitric oxide (NO) and reactive oxygen species (ROS)] and the activation and expression of CD29 as judged by cell-cell adhesion and surface staining experiments. The inhibition was due to the induction of heme oxygenase (HO)-1 in LPS-activated macrophages, since blocking HO-1 activity with ZnPP, an HO-1 specific inhibitor, abolished hydroquinone's NO inhibitory activity. In addition, hydroquinone and inhibitors (wortmannin and LY294002) of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway had very similar inhibitory effects on LPS-induced and CD29-mediated macrophage responses, including the phosphorylation of Akt. Therefore, our data suggest that hydroquinone inhibits macrophage-mediated immune responses by modulating intracellular signaling and protective mechanisms.
Lee
Ji Yeon
JY
School of Biotechnology and Bioengineering, Kangwon National University, Chuncheon 200-701, Korea.
Kim
Joo Young
JY
Lee
Yong Gyu
YG
Shin
Won Cheol
WC
Chun
Taehoon
T
Rhee
Man Hee
MH
Cho
Jae Youl
JY
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001554:Benzene / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology*; D007109:Immunity / Q000187:drug effects*; D019012:Integrin beta1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D000077191:Wortmannin
D000730:Androstadienes; D001554:Benzene; D002867:Chromones; D016207:Cytokines; D051547:Heme Oxygenase-1; D006873:Hydroquinones; D019012:Integrin beta1; D008070:Lipopolysaccharides; D009025:Morpholines; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D000077191:Wortmannin; C017803:zinc protoporphyrin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C031927:hydroquinone