Human β-Defensin 3 Inhibits <i>Porphyromonas Gingivalis</i> Lipopolysaccharide-Induced Oxidative and Inflammatory Responses of Microglia by Suppression of Cathepsins B and L
Recently, the effects of antibacterial peptides are suggested to have therapeutic potential in Alzheimer’s disease. Furthermore, systemic treatment of <i>Porphyromonas gingivalis</i> (<i>Pg</i>) lipopolysaccharide (LPS) induced Alzheimer’s disease-like neuropathological chang...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15099 |
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| author | Erika Inoue Shiyo Minatozaki Yui Katsuta Saori Nonaka Hiroshi Nakanishi |
| author_facet | Erika Inoue Shiyo Minatozaki Yui Katsuta Saori Nonaka Hiroshi Nakanishi |
| author_sort | Erika Inoue |
| collection | DOAJ |
| description | Recently, the effects of antibacterial peptides are suggested to have therapeutic potential in Alzheimer’s disease. Furthermore, systemic treatment of <i>Porphyromonas gingivalis</i> (<i>Pg</i>) lipopolysaccharide (LPS) induced Alzheimer’s disease-like neuropathological changes in middle-aged mice. Then, we examined whether human β-defensins (hBDs), antimicrobial peptides produced by the oral mucosa and salivary glands, can suppress <i>Pg</i> LPS-induced oxidative and inflammatory responses by microglia. hBD3 (1 μM) significantly suppressed <i>Pg</i> LPS-induced production of nitric oxide and interleukin-6 (IL-6) by MG6 cells, a mouse microglial cell line. hBD3 (1 μM) also significantly inhibited <i>Pg</i> LPS-induced expression of IL-6 by HMC3 cells, a human microglial cell line. In contrast, neither hBD1, hBD2 nor hBD4 failed to inhibit their productions. Furthermore, hBD3 suppressed <i>Pg</i> LPS-induced p65 nuclear translocation through the IκBα degradation. <i>Pg</i> LPS-induced expression of IL-6 was significantly suppressed by E64d, a cysteine protease inhibitor, and CA-074Me, a known specific inhibitor for cathepsin B, but not by pepstatin A, an aspartic protease inhibitor. Interestingly, hBD3 significantly inhibited enzymatic activities of recombinant human cathepsins B and L, lysosomal cysteine proteases, and their intracellular activities in MG6 cells. Therefore, hBD3 suppressed oxidative and inflammatory responses of microglia through the inhibition of cathepsins B and L, which enzymatic activities are necessary for the NF-κB activation. |
| first_indexed | 2024-03-09T17:45:41Z |
| format | Article |
| id | doaj.art-9c91987a5506494397ad4cd70617576f |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:45:41Z |
| publishDate | 2022-12-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9c91987a5506494397ad4cd70617576f2023-11-24T11:13:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231509910.3390/ijms232315099Human β-Defensin 3 Inhibits <i>Porphyromonas Gingivalis</i> Lipopolysaccharide-Induced Oxidative and Inflammatory Responses of Microglia by Suppression of Cathepsins B and LErika Inoue0Shiyo Minatozaki1Yui Katsuta2Saori Nonaka3Hiroshi Nakanishi4Faculty of Pharmacy, Yasuda Women’s University, Hiroshima 731-0153, JapanFaculty of Pharmacy, Yasuda Women’s University, Hiroshima 731-0153, JapanFaculty of Pharmacy, Yasuda Women’s University, Hiroshima 731-0153, JapanDepartment of Pharmacology, Faculty of Pharmacy, Yasuda Women’s University, Hiroshima 731-0153, JapanDepartment of Pharmacology, Faculty of Pharmacy, Yasuda Women’s University, Hiroshima 731-0153, JapanRecently, the effects of antibacterial peptides are suggested to have therapeutic potential in Alzheimer’s disease. Furthermore, systemic treatment of <i>Porphyromonas gingivalis</i> (<i>Pg</i>) lipopolysaccharide (LPS) induced Alzheimer’s disease-like neuropathological changes in middle-aged mice. Then, we examined whether human β-defensins (hBDs), antimicrobial peptides produced by the oral mucosa and salivary glands, can suppress <i>Pg</i> LPS-induced oxidative and inflammatory responses by microglia. hBD3 (1 μM) significantly suppressed <i>Pg</i> LPS-induced production of nitric oxide and interleukin-6 (IL-6) by MG6 cells, a mouse microglial cell line. hBD3 (1 μM) also significantly inhibited <i>Pg</i> LPS-induced expression of IL-6 by HMC3 cells, a human microglial cell line. In contrast, neither hBD1, hBD2 nor hBD4 failed to inhibit their productions. Furthermore, hBD3 suppressed <i>Pg</i> LPS-induced p65 nuclear translocation through the IκBα degradation. <i>Pg</i> LPS-induced expression of IL-6 was significantly suppressed by E64d, a cysteine protease inhibitor, and CA-074Me, a known specific inhibitor for cathepsin B, but not by pepstatin A, an aspartic protease inhibitor. Interestingly, hBD3 significantly inhibited enzymatic activities of recombinant human cathepsins B and L, lysosomal cysteine proteases, and their intracellular activities in MG6 cells. Therefore, hBD3 suppressed oxidative and inflammatory responses of microglia through the inhibition of cathepsins B and L, which enzymatic activities are necessary for the NF-κB activation.https://www.mdpi.com/1422-0067/23/23/15099antibacterial peptidecathepsin Bcathepsin Lhuman β-defensinsinterleukin-6lipopolysaccharide |
| spellingShingle | Erika Inoue Shiyo Minatozaki Yui Katsuta Saori Nonaka Hiroshi Nakanishi Human β-Defensin 3 Inhibits <i>Porphyromonas Gingivalis</i> Lipopolysaccharide-Induced Oxidative and Inflammatory Responses of Microglia by Suppression of Cathepsins B and L International Journal of Molecular Sciences antibacterial peptide cathepsin B cathepsin L human β-defensins interleukin-6 lipopolysaccharide |
| title | Human β-Defensin 3 Inhibits <i>Porphyromonas Gingivalis</i> Lipopolysaccharide-Induced Oxidative and Inflammatory Responses of Microglia by Suppression of Cathepsins B and L |
| title_full | Human β-Defensin 3 Inhibits <i>Porphyromonas Gingivalis</i> Lipopolysaccharide-Induced Oxidative and Inflammatory Responses of Microglia by Suppression of Cathepsins B and L |
| title_fullStr | Human β-Defensin 3 Inhibits <i>Porphyromonas Gingivalis</i> Lipopolysaccharide-Induced Oxidative and Inflammatory Responses of Microglia by Suppression of Cathepsins B and L |
| title_full_unstemmed | Human β-Defensin 3 Inhibits <i>Porphyromonas Gingivalis</i> Lipopolysaccharide-Induced Oxidative and Inflammatory Responses of Microglia by Suppression of Cathepsins B and L |
| title_short | Human β-Defensin 3 Inhibits <i>Porphyromonas Gingivalis</i> Lipopolysaccharide-Induced Oxidative and Inflammatory Responses of Microglia by Suppression of Cathepsins B and L |
| title_sort | human β defensin 3 inhibits i porphyromonas gingivalis i lipopolysaccharide induced oxidative and inflammatory responses of microglia by suppression of cathepsins b and l |
| topic | antibacterial peptide cathepsin B cathepsin L human β-defensins interleukin-6 lipopolysaccharide |
| url | https://www.mdpi.com/1422-0067/23/23/15099 |
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