Open AccessUp‐regulation of matrix metalloproteinase‐3 in the dorsal root ganglion of rats with paclitaxel‐induced neuropathy
Author(s) -
Nishida Kentaro,
Kuchiiwa Satoshi,
Oiso Shigeru,
Futagawa Toshitaka,
Masuda Shogo,
Takeda Yasuo,
Yamada Katsushi
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00877.x
Subject(s) - dorsal root ganglion , paclitaxel , matrix metalloproteinase , dorsum , medicine , ganglion , matrix metalloproteinase 9 , matrix (chemical analysis) , anatomy , chemistry , chemotherapy , chromatography
Paclitaxel‐induced painful peripheral neuropathy is a major dose‐limiting factor. Recently, it has been reported that macrophages accumulated in the dorsal root ganglion of paclitaxel‐treated rats, and their activation is suggested to contribute to generation and development of the neuropathy. However, the mechanism for macrophage activation is still unknown. In this study, to explore candidate genes involved in the mechanism for macrophage activation in the dorsal root ganglion of paclitaxel‐treated rats, we developed model rats for paclitaxel‐induced neuropathic pain and performed a microarray assay to analyze the changes of gene expressions in the dorsal root ganglion. Among the genes with changed expression levels, we focused on matrix metalloproteinase‐3 ( MMP‐3 , stromelysin‐1) and CD163 , a macrophage marker. By reverse transcription–polymerase chain reaction, the expression levels of MMP‐3 and CD163 were markedly up‐regulated in paclitaxel‐treated dorsal root ganglion. As a result of immunohistochemical study, large ganglion neurons, but neither Schwann cells nor macrophages, predominantly expressed MMP‐3. This MMP‐3 up‐regulation occurred prior to macrophage accumulation in the dorsal root ganglion. In addition, recombinant MMP‐3 led to the activation of RAW264 macrophages in vitro . Taken together, the up‐regulation of MMP‐3 and following macrophage activation caused in the dorsal root ganglion might be a significant event to trigger a series of reactions developing paclitaxel‐induced peripheral neuropathic pain. ( Cancer Sci 2008; 99: 1618–1625)