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Tsuneyasu Kaisho

Publications and source records attributed to Tsuneyasu Kaisho.

38 records · Page 3Linked to original sources

Toll-like receptors.

The innate immune system in drosophila and mammals senses the invasion of microorganisms using the family of Toll receptors, stimulation of which initiates a range of host defense mechanisms. In drosophila antimicrobial responses rely on two signaling pathways: the Toll pathway and the IMD pathway. In mammals there are at least 10 members of the Toll-like receptor (TLR) family that recognize specific components conserved among microorganisms. Activation of the TLRs leads not only to the induction of inflammatory responses but also to the development of antigen-specific adaptive immunity. The TLR-induced inflammatory response is dependent on a common signaling pathway that is mediated by the adaptor molecule MyD88. However, there is evidence for additional pathways that mediate TLR ligand-specific biological responses.

Adaptor Proteins, Signal Transducing↗

Interleukin-18 inhibits osteolytic bone metastasis by human lung cancer cells possibly through suppression of osteoclastic bone-resorption in nude mice.

Interleukin (IL)-18 exhibits antitumor as well as antiosteoclastogenic activities. These findings suggest that IL-18 is a potential tool for the treatment of cancers with associated osteolytic bone metastasis. We have previously shown that systemic daily administration of recombinant (r) IL-18 inhibits the development of osteolytic bone metastasis by human breast cancer cells. Here we demonstrate that systemic daily administration of rIL-18 (1 microg/mouse/d) for 21 days significantly inhibited the number and the total area of osteolytic bone metastasis by RWGT2 human lung cancer cells in nude mice. No severe adverse effects were observed. Natural killer (NK) cells did not increase in splenocytes from rIL-18-treated mice, and the in vitro NK activity of splenocytes against RWGT2 cells was only weakly enhanced in the presence of IL-18. The administration of rIL-18 made no difference in the growth of subcutaneous tumors, histologic indices (mitotic index, apoptotic index, and Ki-67-labeling index) of subcutaneous tumors or metastatic bone foci, or in the number of osteoclasts along the bone surface adjacent to tumors. Moreover, serum levels of cytokines including interferon-gamma, IL-1alpha, IL-6, tumor necrosis factor-alpha, and granulocyte/macrophage colony-stimulating factor, which regulate bone-resorbing activity of osteoclasts, were evaluated. Among them, IL-6 was remarkably downregulated in rIL-18-treated mice. These findings suggest that IL-18 inhibits osteolytic bone metastasis possibly through suppression of osteoclastic bone-resorption mediated in part by IL-6.

Animals↗