title: MyD88 is a mediator for the activation of Nrf2.
abstract: If not controlled properly, inflammatory response is often detrimental. However, in many cases, it can be self-limited and subsides without inflicting tissue damage. In this study, we tested the hypothesis that inflammatory stimuli can trigger anti-inflammatory response, which may contribute to limiting tissue damage induced by excessive inflammation. We found that treatment of bone marrow-derived macrophages with lipopolysaccharide (LPS) activated NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor that regulates inflammation, leading to expression of Nrf2-regulated genes including NAD(P)H:quinine oxidoreductase 1,glutamyl cysteine ligase catalytic unit and heme oxygenase-1. Suppression of Nrf2 by siRNA significantly diminished the expression of the Nrf2-regulated genes induced by LPS. By using pharmacological, genetic and epigenetic analyses, we found that activation of Nrf2 in response to LPS is dependent on MyD88 but independent of the production of reactive oxygen species. Together, our results show that activation of Nrf2 by MyD88 dependent signaling induced by LPS is an important intrinsic mechanism that limits excessive inflammation.
authors.affiliation: Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
authors.forename: Kyun Ha
authors.initials: KH
authors.lastname: Kim
authors.forename: Ji Hyo
authors.initials: JH
authors.lastname: Lyu
authors.forename: Sung Tae
authors.initials: ST
authors.lastname: Koo
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.forename: Hyeong-Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Kyung-Seop
authors.initials: KS
authors.lastname: Ahn
authors.forename: Ruxana T
authors.initials: RT
authors.lastname: Sadikot
authors.forename: Myungsoo
authors.initials: M
authors.lastname: Joo
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D007249:Inflammation / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species
chemical_list: D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051267:NF-E2-Related Factor 2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D005721:Glutamate-Cysteine Ligase