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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine >
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Absence of CD14 Delays Progression of Prion Diseases Accompanied by Increased Microglial Activation
| Title: | Absence of CD14 Delays Progression of Prion Diseases Accompanied by Increased Microglial Activation |
| Authors: | Sakai, Keiko Browse this author | | Hasebe, Rie Browse this author →KAKEN DB | | Takahashi, Yusuke Browse this author →KAKEN DB | | Song, Chang-Hyun Browse this author | | Suzuki, Akio Browse this author | | Yamasaki, Takeshi Browse this author | | Horiuchi, Motohiro Browse this author →KAKEN DB |
| Issue Date: | Dec-2013 |
| Publisher: | American Society for Microbiology |
| Journal Title: | Journal of Virology |
| Volume: | 87 |
| Issue: | 24 |
| Start Page: | 13433 |
| End Page: | 13445 |
| Publisher DOI: | 10.1128/JVI.02072-13 |
| Abstract: | Prion diseases are fatal neurodegenerative disorders characterized by accumulation of PrPSc, vacuolation of neurons and neuropil, astrocytosis, and microglial activation. Upregulation of gene expressions of innate immunity-related factors, including complement factors and CD14, is observed in the brains of mice infected with prions even in the early stage of infections. When CD14 knockout (CD14(-/-)) mice were infected intracerebrally with the Chandler and Obihiro prion strains, the mice survived longer than wild-type (WT) mice, suggesting that CD14 influences the progression of the prion disease. Immunofluorescence staining that can distinguish normal prion protein from the disease-specific form of prion protein (PrPSc) revealed that deposition of PrPSc was delayed in CD14(-/-) mice compared with WT mice by the middle stage of the infection. Immunohistochemical staining with Iba1, a marker for activated microglia, showed an increased microglial activation in prion-infected CD14(-/-) mice compared to WT mice. Interestingly, accompanied by the increased microglial activation, anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta) appeared to be expressed earlier in prion-infected CD14(-/-) mice. In contrast, IL-1 beta expression appeared to be reduced in the CD14(-/-) mice in the early stage of infection. Double immunofluorescence staining demonstrated that CD11b- and Iba1-positive microglia mainly produced the anti-inflammatory cytokines, suggesting anti-inflammatory status of microglia in the CD14(-/-) mice in the early stage of infection. These results imply that CD14 plays a role in the disease progression by suppressing anti-inflammatory responses in the brain in the early stage of infection. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/56527 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 堀内 基広
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