Open AccessChemical inducer of regucalcin attenuates lipopolysaccharide‐induced inflammatory responses in pancreatic MIN6 β‐cells and RAW264.7 macrophages
Author(s) -
Murata Tomiyasu,
Hashimoto Kazunori,
Kohno Susumu,
Takahashi Chiaki,
Yamaguchi Masayoshi,
Ito Chihiro,
Masataka Itoigawa,
Kojima Roji,
Hikita Kiyomi,
Kaneda Norio
Publication year - 2022
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13321
Subject(s) - lipopolysaccharide , nitric oxide , apoptosis , cytotoxicity , tumor necrosis factor alpha , microbiology and biotechnology , inflammation , oxidative stress , chemistry , reactive oxygen species , cell culture , pharmacology , biology , biochemistry , immunology , in vitro , genetics , organic chemistry
We previously isolated derrisfolin A, a novel rotenoid derivative, from the stems of Derris trifoliata Lour. (Leguminosae). Here, we report that derrisfolin A induces the expression of endogenous regucalcin (RGN) protein in both pancreatic MIN6 β ‐ cells and RAW264.7 macrophages. Induction of RGN expression by derrisfolin A or retrovirus‐mediated gene transfer in MIN6 cells and RAW264.7 macrophages significantly decreased lipopolysaccharide (LPS)‐induced mRNA expression of Nos2 , Il1b , and Tnf via nuclear factor‐κB activation; reduced LPS‐induced apoptosis in MIN6 cells, accompanied by decreased production of nitric oxide, interleukin‐1β, and tumor necrosis factor‐α; and attenuated generation of LPS‐induced reactive oxygen species, malondialdehyde, and 3‐nitrotyrosine in MIN6 cells. Additionally, in co‐cultures of MIN6 cells with RAW264.7 macrophages in the presence of LPS, induction of RGN expression by derrisfolin A or retrovirus‐mediated gene transfer in RAW264.7 macrophages attenuated apoptosis and oxidative/nitrosative stress in MIN6 cells. These results suggest that the induction of RGN expression in MIN6 cells was effective in suppressing LPS‐induced inflammatory cytotoxicity and that in co‐culture conditions, the induction of RGN expression in RAW264.7 macrophages blocked LPS‐induced paracrine effects of RAW264.7 macrophages on inflammatory cytotoxicity in MIN6 cells. Our findings suggest that derrisfolin A, a chemical inducer of RGN, might be useful for developing a new drug against macrophage‐associated β‐cell inflammation in type 2 diabetes.