Dataset Information

Chemical inducer of regucalcin attenuates lipopolysaccharide-induced inflammatory responses in pancreatic MIN6 β-cells and RAW264.7 macrophages.

ABSTRACT: 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.

SUBMITTER: Murata T

PROVIDER: S-EPMC8727933 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Context Torin2 has various pharmacological properties. However, its anti-inflammatory activity has not been reported. Objective This study focused on the potential anti-inflammatory properties of Torin2 in lipopolysaccharide (LPS)-evoked RAW264.7 murine macrophages. The study aimed to shed light on the molecular mechanisms that ameliorate these effects. Methods Torin2 was applied to 100 ng/mL lipopolysaccharide-induced RAW 264.7 macrophages in vitro. Nitric oxide (NO) levels were detected using the Griess reagent kit. Prostaglandin E2 (PGE2), pro-inflammatory cytokines interleukin (IL)-1β, interleukin (IL)-6, and tumor necrosis factor in the supernatant fraction were determined using enzyme-linked immunosorbent assay (ELISA). Gene expression of pro-inflammatory cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) were tested using real-time quantitative polymerase chain reaction (qPCR). Cyclooxygenase-2 and inducible nitric oxide synthase proteins, phosphorylation of mitogen-activated protein kinase (MAPK) subgroups, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, I-kappa-B-alpha (IκBα), and nuclear factor-kappa-B (NF-κB), and activation in extracts were detected via western blotting. Nuclear factor-kappa-B/p65 nuclear translocation was tested using an immunofluorescence assay. Results The results demonstrated that pre-treatment with Torin2 profoundly attenuated the lipopolysaccharide-stimulated levels of nitric oxide and prostaglandin E2, pro-inflammatory cytokines, messenger ribonucleic acid (mRNA), and protein expression of cyclooxygenase-2 and inducible nitric oxide synthase. Collectively, Torin2 pre-treatment notably weakened lipopolysaccharide-induced damage by reducing the phosphorylation of nuclear factor-kappa-B, p38, c-Jun N-terminal kinase, extracellular signal-regulated kinase proteins, and nuclear factor-kappa-B/p65 nuclear translocation. Conclusion Numerous pieces of evidence indicated that Torin2 reversed inflammatory activation by regulating nuclear factor-kappa-B and mitogen-activated protein kinase signaling pathways and provided a tentative potential candidate for preventing and treating inflammatory diseases. Torin2; RAW264.7 murine macrophages; Lipopolysaccharide; Anti-inflammation; Mechanisms.

Dataset Information

Chemical inducer of regucalcin attenuates lipopolysaccharide-induced inflammatory responses in pancreatic MIN6 β-cells and RAW264.7 macrophages.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets