Dataset Information

β2 ADRENERGIC SIGNALING STIMULATES EARLY IL-1β SECRETION IN MACROPHAGES BY INDUCING MAPK-DEPENDENT Il1b TRANSCRIPTION [RNA-Seq]

ABSTRACT: Activating β2 adrenergic receptor (β2AR) on macrophages inhibits the expression of several proinflammatory cytokines, a phenomenon primarily associated with NF-κB inhibition. IL-1β is a hallmark inflammatory cytokine, and NF-κB plays a role in the transcriptional activation of Il1b in the priming phase of the NLRP3 inflammasome. Here, we report that contrarily to expectations, β2AR signaling stimulated transcription of the Il1b gene, either alone or in combination with TLR ligands. Moreover, in vivo experiments demonstrated that mice with increased sympathetic tonus (Adra2ac-/-) produced higher levels of IL-1β in a β2AR-dependent manner during alum-induced peritonitis. Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-Seq) experiments, genome-wide analyses of clustered genomic regions and the utilization of pharmacological inhibitors revealed that β2AR-induced Il1b expression occurs in PKA-, MAP Kinases- and AP-1-dependent manner. Our findings describe that β2AR signaling can regulate macrophage effector function in a complex way that may involve gene-specific mechanisms increasing the expression of pro-inflammatory cytokines such as IL-1β.

ORGANISM(S): Mus musculus

PROVIDER: GSE278577 | GEO | 2025/12/19

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Colitis is the common pathological lesion of inflammatory bowel diseases, the major chronic inflammatory diseases of intestinal tracts in humans. In this study, we investigated the therapeutic effects of ginger extract and its component zingerone in mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Mice were administered with TNBS and/or various amounts of ginger and zingerone by an intrarectal route. The severity of colitis was evaluated by colonic weight/length ratio, macroscopic lesion, and histological examination. The mechanisms of ginger and zingerone were further elucidated by DNA microarray, ex vivo imaging, and immunohistochemical staining. Our data showed that treatment with ginger extract and zingerone ameliorated TNBS-induced colonic inflammation and injury in a dose-dependent manner. Pathway analysis of ginger- and zingerone-regulated gene expression profiles showed that ginger and zingerone significantly regulated cytokine-related pathways. Network analysis showed that nuclear factor-κB (NF-κB) and interleukin-1β (IL-1β) were key molecules involved in the expression of ginger- and zingerone-affected genes. Ex vivo imaging and immunohistochemical staining further verified that ginger and zingerone suppressed TNBS-induced NF-κB activation and decreased the NF-κB and IL-1β protein levels in the colon. In conclusion, our data showed that ginger improved the TNBS-induced colitis in mice via modulation of NF-κB activity and IL-1β signaling pathway. Moreover, zingerone might be the active component of ginger responsible for the amelioration of colitis induced by TNBS. A total of 24 mice was randomly divided into four groups of six mice: mock, mice were given with 0.1 ml of 50% ethanol; TNBS, mice were given with 250 mg/kg TNBS in 0.1 ml of 50% ethanol; TNBS/ginger, mice were administered with mixtures containing 250 mg/kg TNBS and various amounts of ginger extract in 0.1 ml of 50% ethanol; TNBS/zingerone, mice were given with mixtures containing 250 mg/kg TNBS and various amounts of zingerone in 0.1 ml of 50% ethanol. Mice were sacrificed seven days later for histochemical staining, RNA extraction, and ex vivo imaging.

Dataset Information

β2 ADRENERGIC SIGNALING STIMULATES EARLY IL-1β SECRETION IN MACROPHAGES BY INDUCING MAPK-DEPENDENT Il1b TRANSCRIPTION [RNA-Seq]

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets