Peptidoglycan-Like Components in Z-100, Extracted from Mycobacterium tuberculosis Strain Aoyama B, Increase IL-12p40 via NOD2
Background. Z-100 is a hot-water extract of the human-type Mycobacterium tuberculosis strain Aoyama B. While Z-100’s macrophage-mediated immunomodulatory effects have been reported, the mechanistic details have not been fully clarified. Here, we studied the immunomodulatory effects of Z-100 on mouse...
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| Format: | Article |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/3530937 |
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| author | Takayuki Horii Yuki Orikawa Yuta Ohira Runa Eta Uiko Tominaga Takanori Sato Takao Tanaka |
| author_facet | Takayuki Horii Yuki Orikawa Yuta Ohira Runa Eta Uiko Tominaga Takanori Sato Takao Tanaka |
| author_sort | Takayuki Horii |
| collection | DOAJ |
| description | Background. Z-100 is a hot-water extract of the human-type Mycobacterium tuberculosis strain Aoyama B. While Z-100’s macrophage-mediated immunomodulatory effects have been reported, the mechanistic details have not been fully clarified. Here, we studied the immunomodulatory effects of Z-100 on mouse bone marrow-derived cells, human CD14+ cells, and skin. Methods. Mouse bone marrow-derived cells and CD14+ cells were cultured in the presence of granulocyte-macrophage colony-stimulating factor, differentiated into macrophage-like cells, and then stimulated with Z-100. Furthermore, since Z-100 is subcutaneously administered clinically, we injected Z-100 into mice and measured gene expression in the skin. Results. While Z-100 stimulation increased the production of interleukin- (IL-) 12p40 and IL-1β in mouse bone marrow-derived macrophages, levels of IL-1β were low. In contrast, TNF-α production did not increase. Meanwhile, stimulation of human CD14+ cells with Z-100 increased production of IL-12p40, TNF-α, and IL-1β. Because Z-100 appeared to have the most stable effect on IL-12p40, we examined the components of Z-100 that induce IL-12p40 production. We found that Z-100 contained peptidoglycan-like components. In addition, an siRNA study showed that Z-100 increased the production of IL-12p40 via nucleotide-binding oligomerization domain 2 (NOD2). Further, subcutaneous administration of Z-100 to mice significantly elevated expression of IL-12p40 and IL-1β and showed a trend towards increasing TNF-α in the skin. Conclusion. Z-100 induced the production of immunomodulatory cytokines from various types of macrophages and specifically increased IL-12p40 production through peptidoglycan-like components via NOD2. |
| format | Article |
| id | doaj-art-99b69d2486094f4d9d1ed31f14ddd269 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-99b69d2486094f4d9d1ed31f14ddd2692025-02-03T06:11:56ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/3530937Peptidoglycan-Like Components in Z-100, Extracted from Mycobacterium tuberculosis Strain Aoyama B, Increase IL-12p40 via NOD2Takayuki Horii0Yuki Orikawa1Yuta Ohira2Runa Eta3Uiko Tominaga4Takanori Sato5Takao Tanaka6Central Research LaboratoriesCentral Research LaboratoriesCentral Research LaboratoriesCentral Research LaboratoriesCentral Research LaboratoriesCentral Research LaboratoriesCentral Research LaboratoriesBackground. Z-100 is a hot-water extract of the human-type Mycobacterium tuberculosis strain Aoyama B. While Z-100’s macrophage-mediated immunomodulatory effects have been reported, the mechanistic details have not been fully clarified. Here, we studied the immunomodulatory effects of Z-100 on mouse bone marrow-derived cells, human CD14+ cells, and skin. Methods. Mouse bone marrow-derived cells and CD14+ cells were cultured in the presence of granulocyte-macrophage colony-stimulating factor, differentiated into macrophage-like cells, and then stimulated with Z-100. Furthermore, since Z-100 is subcutaneously administered clinically, we injected Z-100 into mice and measured gene expression in the skin. Results. While Z-100 stimulation increased the production of interleukin- (IL-) 12p40 and IL-1β in mouse bone marrow-derived macrophages, levels of IL-1β were low. In contrast, TNF-α production did not increase. Meanwhile, stimulation of human CD14+ cells with Z-100 increased production of IL-12p40, TNF-α, and IL-1β. Because Z-100 appeared to have the most stable effect on IL-12p40, we examined the components of Z-100 that induce IL-12p40 production. We found that Z-100 contained peptidoglycan-like components. In addition, an siRNA study showed that Z-100 increased the production of IL-12p40 via nucleotide-binding oligomerization domain 2 (NOD2). Further, subcutaneous administration of Z-100 to mice significantly elevated expression of IL-12p40 and IL-1β and showed a trend towards increasing TNF-α in the skin. Conclusion. Z-100 induced the production of immunomodulatory cytokines from various types of macrophages and specifically increased IL-12p40 production through peptidoglycan-like components via NOD2.http://dx.doi.org/10.1155/2022/3530937 |
| spellingShingle | Takayuki Horii Yuki Orikawa Yuta Ohira Runa Eta Uiko Tominaga Takanori Sato Takao Tanaka Peptidoglycan-Like Components in Z-100, Extracted from Mycobacterium tuberculosis Strain Aoyama B, Increase IL-12p40 via NOD2 Journal of Immunology Research |
| title | Peptidoglycan-Like Components in Z-100, Extracted from Mycobacterium tuberculosis Strain Aoyama B, Increase IL-12p40 via NOD2 |
| title_full | Peptidoglycan-Like Components in Z-100, Extracted from Mycobacterium tuberculosis Strain Aoyama B, Increase IL-12p40 via NOD2 |
| title_fullStr | Peptidoglycan-Like Components in Z-100, Extracted from Mycobacterium tuberculosis Strain Aoyama B, Increase IL-12p40 via NOD2 |
| title_full_unstemmed | Peptidoglycan-Like Components in Z-100, Extracted from Mycobacterium tuberculosis Strain Aoyama B, Increase IL-12p40 via NOD2 |
| title_short | Peptidoglycan-Like Components in Z-100, Extracted from Mycobacterium tuberculosis Strain Aoyama B, Increase IL-12p40 via NOD2 |
| title_sort | peptidoglycan like components in z 100 extracted from mycobacterium tuberculosis strain aoyama b increase il 12p40 via nod2 |
| url | http://dx.doi.org/10.1155/2022/3530937 |
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