Dataset Information

Identification of anti-inflammatory effects of Protaetia brevitarsis seulensis larvae in IL-1β-induced chondrosarcoma cells based on systematic transcriptome analysis

ABSTRACT: Osteoarthritis (OA) is a complex degenerative joint and multi-factorial disease. Developing new targeting strategies that can be used to understand its molecular mechanisms is critical owing to the difficulty in treating OA. Protaetia brevitarsis seulensis larvae present high therapeutic value; however, the presence of various active compounds and the multi-factorial risk factors for OA renders the precise mechanisms of action unclear. We screened the key mechanisms of action of P. brevitarsis seulensis larvae aqueous extract (PBSL) and its compounds using systematic transcriptome analysis. Major mechanisms and transcription factors of PBSL were analyzed by profiling gene expression changes in interleukin (IL)-1β-induced human chondrosarcoma cell (SW1353) treated with PBSL. Furthermore, an in vitro assay was perfomed to validate the efficacy of the novel mechanism and targets of PBSL. PBSL exerted anti-inflammatory effects on SW1353 cells by regulating many molecular pathways. The IL-6/JAK/STAT3 pathway was significantly downregulated by PBSL, and STAT3 was identified as a major transcription factor regulating PBSL-induced target gene expression. Furthermore, we found that among the six PBSL compounds, the major compound was regulated by the IL-6/JAK/STAT3 pathway. Our findings reinforce the idea that inhibiting the IL-6/JAK/STAT3 pathway is a therapeutic target for treating OA, providing potential novel mechanisms and transcription factors for PBSL and its active compounds against OA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268400 | GEO | 2025/05/06

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The activated B cell-like (ABC) subgroup of diffuse large B cell lymphoma (DLBCL) is characterized by constitutive activation of the NF-ÃªB pathway. Here we show that the NF- ÃªB pathway induces the expression of the cytokines IL-6 and IL-10 in ABC DLBCL cell lines, which also have high levels of total and phosphorylated STAT3 protein, suggesting autocrine signaling. Using RNA interference for STAT3, we defined a gene expression signature of IL-6 and IL-10 signaling through STAT3. Based on this signature, we constructed a molecular predictor of STAT3 signaling that defined a subset of ABC DLBCL tumors with high expression of STAT3, IL-6 and/or IL-10, and their downstream targets. Although the STAT3-high and STAT3-low subsets had equivalent expression of genes that distinguish ABC DLBCL from GCB DLBCL, STAT3-high ABC DLBCLs had higher expression of signatures that reflected NF-kB activity, proliferation, and glycolysis. A smallmolecule inhibitor of JAK signaling, which blocked STAT3 signature expression, was toxic only for ABC DLBCL lines, and synergized with an inhibitor of NF-kB signaling. These findings suggest that the biological interplay between the STAT3 and NF-kB pathways may be exploited for the treatments of a subset of ABC DLBCLs. Activated B cell-like (ABC) subgroup of diffuse large B cell lymphoma (DLBCL) cell lines were used as model systems to study the cytokine pathways in these cells. We expressed inducible IkB super-repressor for 1 to 24 hours to identify NF-kB target genes in OCI-Ly3 and OCI-Ly10 cells for a total of 13 arrays with replicates of each time point. We treated OCI-Ly3 cells with IL-10 for 1 to 96 hours for a total of 10 arrays with replicates of each time point. We treated OCI-Ly10 cells with IL-6 for 30 minutes to 24 hours for a total of 8 arrays with replicates of each time point. OCI-Ly10 cells transfected with no siRNA versus STAT3-siRNA for 8, 24, or 48 hours for a total of 5 arrays with replicates for 24 and 48 hours. We treated OCI-Ly10 cells with JAK inhibitor I for 3 and 6 hours for a total of 4 arrays with replicates of each time point.

Project description:Rheumatoid arthritis (RA) fibroblast‐like synoviocytes (FLS) derived from hip and knee have distinctive DNA methylation and transcriptome patterns in interleukin (IL)‐6 signaling and Janus kinase (JAK)–signal transducers and activators of transcription (STAT) pathways. To determine the functional effects of these joint‐specific signatures, we evaluated how RA hip and knee FLS differ in their response to IL‐6.Hip or knee RA FLS were obtained after arthroplasty. Previously published datasets on epigenetic landscape of FLS were mined to identify joint‐specific IL‐6–related epigenomic differences. RNA sequencing was performed on five RA hip and five knee FLS treated with or without IL‐6. Differential gene expression was determined using edgeR software. STAT3 phosphorylation was measured using bead assays. Sensitivity to tofacitinib was evaluated by measuring CCL2 inhibition using quantitative polymerase chain reaction. Assay for Transposase‐Accessible Chromatin sequencing and histone chromatin immunoprecipitation sequencing datasets from RA FLS were analyzed to identify epigenomic differences between hip and knee. Differential chromatin accessibility was associated with IL‐6, IL‐6R, and JAK1 genes. H3K27ac was also differentially marked at other JAK‐STAT–related genes, including STAT3‐STAT5A region. Principal component analysis of RNA sequencing data confirmed segregation between RA hip and knee FLS under basal conditions, that persisted following IL‐6 treatment. STAT3 phosphorylation after IL‐6 was significantly higher in knee than hip FLS and was highly correlated with JAK1 protein levels. Knee FLS were less sensitive to the JAK inhibitor tofacitinib than hip FLS. RA hip and knee FLS have distinct transcriptomes, epigenetic marks, and STAT3 activation patterns in the IL‐6 pathway. These joint‐specific differences might contribute to a differential clinical response in individual joints to targeted therapies such as JAK inhibitors.

Dataset Information

Identification of anti-inflammatory effects of Protaetia brevitarsis seulensis larvae in IL-1β-induced chondrosarcoma cells based on systematic transcriptome analysis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets