| First Author | Katsunuma K | Year | 2015 |
| Journal | Mol Immunol | Volume | 64 |
| Issue | 1 | Pages | 218-27 |
| PubMed ID | 25499802 | Mgi Jnum | J:223251 |
| Mgi Id | MGI:5648593 | Doi | 10.1016/j.molimm.2014.11.017 |
| Citation | Katsunuma K, et al. (2015) Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, promotes TNF-alpha production via nucleotide-binding oligomerization domain containing 2 (Nod2)-dependent NF-kappaB activation in RAW264.7 cells. Mol Immunol 64(1):218-27 |
| abstractText | Macrophages are a major component of the innate immune system, and the cytokines they secrete are involved in antitumor responses. Z-100 is obtained from hot-water extract of human-type Mycobacterium tuberculosis strain Aoyama B and activates the innate immune response. However, while Z-100 is known to modulate macrophage activity, the mechanism behind this modulation is not fully understood. We evaluated the effects of Z-100 on the murine macrophage cell line RAW264.7. Tumor necrosis factor-alpha (TNF-alpha) production from RAW264.7 cells was strongly induced by Z-100 and interferon-gamma (IFN-gamma) stimulation but only weakly induced by Z-100 alone. Quantitative gene expression analysis showed that nucleotide-binding oligomerization domain containing 2 (Nod2) expression was up-regulated by IFN-gamma treatment in RAW264.7 cells while Z-100-induced TNF-alpha production was attenuated by Nod2 gene silencing. Further, componential analysis demonstrated that muramic acid and amino acids distinctive of muramyl dipeptide (MDP) were contained within Z-100 and Z-100Fr I, the low-molecular-weight fraction containing components <3 kDa in size. In addition, Z-100Fr I enhanced TNF-alpha production in RAW264.7 cells and promoted NOD2-dependent nuclear factor-kappa B (NF-kappaB) activation in murine NOD2-expressing SEAP reporter HEK293 (HEK-Blue-mNOD2) cells. Taken together, these results suggest that Z-100 contains MDP-like molecules and augments NF-kappaB signaling via the direct activation of Nod2 in macrophages, which might be one mechanism driving the innate immune responses induced by Z-100 in cancer immunotherapy. |
