Authorship：Lead author   Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Lipopolysaccharide (LPS) tolerance can be recognized as a modulation of innate immune responses rather than merely a hyporesponsiveness to LPS, with CD14 being crucial for both LPS uptake and LPS signaling. In this study, we observed that LPS-tolerant mouse macrophage-like cells, in which LPS-induced TNF-α and IFN-β production was suppressed, exhibited a dramatic increase in surface CD14 expression. Also, we found that LPS uptake was enhanced in LPS-tolerant mouse macrophage-like cells, but not when treated with an anti-CD14 antibody. While previous studies have reported increased CD14 expression and enhanced LPS uptake in LPS-tolerant cells, our findings reveal that overexpressed CD14 in LPS-tolerant mouse macrophage-like cells is responsible for the enhanced LPS uptake in these cells.

DOI： 10.1002/2211-5463.70261

PubMed

Authorship：Lead author   Publishing type：Research paper (scientific journal)  

Abstract

The α-helical antimicrobial peptide Kn2-7 enhances the activation of mouse macrophage-like RAW264.7 induced by DNA containing unmethylated cytosine-guanine motifs (CpG DNA). This enhancement is related to increased cellular uptake of DNA by Kn2-7, but the relevant properties of Kn2-7 are unknown. Physicochemical property analysis revealed that Kn2-7 has high amphipathicity. In contrast, the α-helical antimicrobial peptide L5, which increases the cellular uptake of CpG DNA but does not enhance CpG DNA-induced activation, has low amphipathicity. Kn2-7 derivatives with decreased amphipathicity but the same amino acid composition as Kn2-7 did not enhance CpG DNA-induced activation. On the other hand, L5 derivatives with high amphipathicity but the same amino acid composition as L5 enhanced CpG DNA-induced activation. Cellular uptake of DNA was not increased by the L5 derivatives, indicating that high amphipathicity does not affect DNA uptake. Furthermore, α-helical peptides with reversed sequences relative to the Kn2-7 and L5 derivatives with high amphipathicity were synthesized. The reversed-sequence peptides, which had the same amphipathicity but different amino acid sequences from their counterparts, enhanced CpG DNA-induced activation. Taken together, these observations indicate that the high amphipathicity of α-helical peptides enhances the CpG DNA-induced activation of RAW264.7.

DOI： 10.1038/s41598-024-67166-8

Other URL： https://www.nature.com/articles/s41598-024-67166-8

Publishing type：Research paper (scientific journal)  

Abstract

Inhibition of amyloid-β peptide (Aβ) accumulation in the brain is a promising approach for treatment of Alzheimer’s disease (AD). Aβ is produced by β-secretase and γ-secretase in endosomes via sequential proteolysis of amyloid precursor protein (APP). Aβ and APP have a common feature to readily cluster to form multimers. Here, using multivalent peptide library screens, we identified a tetravalent peptide, LME-tet, which binds APP and Aβ via multivalent interactions. In cells, LME-tet-bound APP in the plasma membrane is transported to endosomes, blocking Aβ production through specific inhibition of β-cleavage, but not γ-cleavage. LME-tet further suppresses Aβ aggregation by blocking formation of the β-sheet conformation. Inhibitory effects are not observed with a monomeric peptide, emphasizing the significance of multivalent interactions for mediating these activities. Critically, LME-tet efficiently reduces Aβ levels in the brain of AD model mice, suggesting it may hold promise for treatment of AD.

DOI： 10.1038/s42003-023-04771-9

Other URL： https://www.nature.com/articles/s42003-023-04771-9

Authorship：Lead author   Publishing type：Research paper (scientific journal)  

DOI： 10.1248/bpbreports.4.2_55

Authorship：Lead author   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.bbrc.2020.07.013

私は学部生時代に研究の魅力に触れて博士課程進学を決意したが、その選択に不安もあった。そうした中、本事業に採択されたことで、自分を支えてくれる人の存在を実感でき、学位取得への大きな励みとなった。学位取得後の現在もこの経験が自信となり、研究活動を推進する大きな原動力となっている。本事業は経済的支援にとどまらず、研究生活における精神的な支えにもなるため、進学を考えている方には積極的に挑戦することをおすすめしたい。

DOI： 10.14894/faruawpsj.61.10_939_2

DOI： 10.24753/jeiis.26.0_17

J-GLOBAL

CiNii Research

Other URL： https://ndlsearch.ndl.go.jp/books/R000000004-I033931088

CiNii Research

Other URL： https://ndlsearch.ndl.go.jp/books/R000000004-I033021107