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71.
Koutarou Nakamura Seiichiro Sakai Jun Tsuyama Akari Nakamura Kento Otani Kumiko Kurabayashi Yoshiko Yogiashi Hisao Masai Takashi Shichita 《PLoS biology》2021,19(5)
Inflammation is implicated in the onset and progression of various diseases, including cerebral pathologies. Here, we report that DJ-1, which plays a role within cells as an antioxidant protein, functions as a damage-associated molecular pattern (DAMP) and triggers inflammation if released from dead cells into the extracellular space. We first found that recombinant DJ-1 protein induces the production of various inflammatory cytokines in bone marrow–derived macrophages (BMMs) and dendritic cells (BMDCs). We further identified a unique peptide sequence in the αG and αH helices of DJ-1 that activates Toll-like receptor 2 (TLR2) and TLR4. In the ischemic brain, DJ-1 is released into the extracellular space from necrotic neurons within 24 h after stroke onset and makes direct contact with TLR2 and TLR4 in infiltrating myeloid cells. Although DJ-1 deficiency in a murine model of middle cerebral artery occlusion did not attenuate neuronal injury, the inflammatory cytokine expression in infiltrating immune cells was significantly decreased. Next, we found that the administration of an antibody to neutralize extracellular DJ-1 suppressed cerebral post-ischemic inflammation and attenuated ischemic neuronal damage. Our results demonstrate a previously unknown function of DJ-1 as a DAMP and suggest that extracellular DJ-1 could be a therapeutic target to prevent inflammation in tissue injuries and neurodegenerative diseases.Intracellular expression of the antioxidant protein DJ-1 has previously been shown to be neuroprotective. This study reveals that extracellularly released DJ-1 from necrotic neurons is a trigger of sterile inflammation that promotes neuronal injury and neurological deficits after ischemic stroke. 相似文献
72.
Miriam R Faria Mara S Hoshida Eloisa AV Ferro Francesca Ietta Luana Paulesu Estela Bevilacqua 《Reproductive biology and endocrinology : RB&E》2010,8(1):95
Background
Macrophage migration inhibitory factor (MIF) has special pro-inflammatory roles, affecting the functions of macrophages and lymphocytes and counter-regulating the effects of glucocorticoids on the immune response. The conspicuous expression of MIF during human implantation and early embryonic development also suggests this factor acts in reproductive functions. The overall goal of this study was to evaluate Mif expression by trophoblast and embryo placental cells during mouse pregnancy. 相似文献73.
Yoshihisa Takaishi Minoru Uda Takashi Ohashi Kimiko Nakano Koutarou Murakami Toshiaki Tomimatsu 《Phytochemistry》1991,30(12):4117-4120
A new glycoside of ergosta-7,22-diene-3,5,6-triol was isolated from the dry fruiting body of Hericum erinacens and the structure was established by chemical and spectroscopic means. Six ergosterol derivatives were also isolated from H. erinacens. 相似文献