Caspase-3 targets pro-interleukin-1β (IL-1β) to restrict inflammation.

The interleukin (IL)-1 family of cytokines plays a pivotal role in immune responses. Among the members of IL-1 family, IL-1β is synthesized as an inactive precursor (pro-IL-1β) and becomes active upon cleavage, which is typically facilitated by inflammasomes through caspase-1. In our research, we explored the potential role of caspase-3 in the cleavage of pro-IL-1β and found that caspase-3 cleaves pro-IL-1β, specifically at Asp26.

Peiminine Exerts Its Anti-Acne Effects by Regulating the NF-κB Pathway.

Peiminine is the main natural alkaloid compound extracted from the Chinese herb Fritillaria. Although peiminine is known for its antioxidant and anti-inflammatory effects in conditions such as mastitis and arthritis, its impact on inflammation induced by () has not been explored. The aim of this study was to investigate the effect of peiminine on -induced inflammatory responses in the skin and to identify the underlying mechanism involved.

Pyrrolidine Dithiocarbamate Suppresses -Induced Skin Inflammation.

(), a Gram-positive anaerobic bacterium, proliferates in hair follicles and pores and causes inflammation in the skin of young people. The rapid growth of triggers macrophages to secrete proinflammatory cytokines. Pyrrolidine dithiocarbamate (PDTC) is a thiol compound that exerts antioxidant and anti-inflammatory effects.

Cynanoside F Controls Skin Inflammation by Suppressing Mitogen-Activated Protein Kinase Activation.

Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied by severe itching and dry skin. Currently, the incidence of AD due to excessive activation of immune cells by various environmental factors is increasing worldwide, and research on inflammatory response inhibitors with fewer side effects is continuously needed. Cynanoside F (CF) is one of the pregnane-type compounds in the root of , an oriental medicinal herb that has been shown to have antioxidant, antitumor, and anti-inflammatory effects.

and Its Phenolic Constituent Sinapic Acid Target Regulator of Calcineurin 1 (RCAN1) to Control Skin Inflammation.

Atopic dermatitis (AD) is a common inflammatory skin disorder, and numerous pharmacological approaches are employed to reduce symptoms. Natural products of plant-derived materials have been accepted as complementary therapy for the treatment of a wide range of inflammatory diseases. (CA) is an oriental medicinal herb used in the treatment of acute urinary infection, febrile diseases, and laryngopharyngitis.

MAP kinase/ERK kinase 1 (MEK1) phosphorylates regulator of calcineurin 1 (RCAN1) to regulate neuronal differentiation.

Regulator of calcineurin 1 (RCAN1) is located close to the Down syndrome critical region (DSCR) on human chromosome 21 and is related to the Down syndrome (DS) phenotype. To identify a novel binding partner of RCAN1, we performed yeast two-hybrid screening and identified mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase (ERK) kinase 1 (MEK1) as a partner. MEK1 was able to bind and phosphorylate RCAN1 in vitro and in vivo.

Sinapic Acid Controls Inflammation by Suppressing NLRP3 Inflammasome Activation.

A natural phenolic acid compound, sinapic acid (SA), is a cinnamic acid derivative that contains 3,5-dimethoxyl and 4-hydroxyl substitutions in the phenyl ring of cinnamic acid. SA is present in various orally edible natural herbs and cereals and is reported to have antioxidant, antitumor, anti-inflammatory, antibacterial, and neuroprotective activities. Although the anti-inflammatory function of SA has been reported, the effect of SA on the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome has not been explored.

Suppression of -Induced Skin Inflammation by Extract and Its Major Constituent Eucalyptol.

Acne is an inflammatory skin disorder in puberty with symptoms including papules, folliculitis, and nodules. () is the main anaerobic bacteria that cause acne. It is known to proliferate within sebum-blocked skin hair follicles.

Laurus nobilis leaf extract controls inflammation by suppressing NLRP3 inflammasome activation.

Laurus nobilis Linn. (Lauraceae), commonly known as Bay, has been used as a traditional medicine in the Mediterranean and Europe to treat diverse immunological disorders. Although the effects of L.

Pyrrolidine dithiocarbamate (PDTC) inhibits inflammatory signaling via expression of regulator of calcineurin activity 1 (RCAN1): Anti-inflammatory mechanism of PDTC through RCAN1 induction.

Pyrrolidine dithiocarbamate (PDTC) is a thiol compound that elicits anti-inflammatory effects by inhibiting NF-κB signaling. In this study, we report that regulator of calcineurin activity 1 (RCAN1) expression is induced by PDTC treatment and that increased RCAN1 expression is dependent on the generation of reactive oxygen species (ROS) and activation of p38 MAPK and JNK signaling. We also report that the ability of PDTC to induce RCAN1 is mediated by activator protein-1 (AP-1)-dependent gene transcription, and identified a functional AP-1 binding site in the RCAN1 promoter by producing mutations and conducting chromatin immunoprecipitation (ChIP) analyses.

Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Targets Down Syndrome Candidate Region 1 (DSCR1/RCAN1) to control Neuronal Differentiation.

Pituitary adenylate cyclase-activating peptide (PACAP) is a neurotrophic peptide involved in a wide range of nervous functions, including development, differentiation, and survival, and various aspects of learning and memory. Here we report that PACAP induces the expression of regulator of calcineurin 1 (RCAN1, also known as DSCR1), which is abnormally expressed in the brains of Down syndrome patients. Increased RCAN1 expression is accompanied by activation of the PKA-cAMP response element-binding protein pathways.

PKA regulates calcineurin function through the phosphorylation of RCAN1: identification of a novel phosphorylation site.

Calcineurin is a calcium/calmodulin-dependent phosphatase that has been implicated in T cell activation through the induction of nuclear factors of activated T cells (NFAT). We have previously suggested that endogenous regulator of calcineurin (RCAN1, also known as DSCR1) is targeted by protein kinase A (PKA) for the control of calcineurin activity. In the present study, we characterized the PKA-mediated phosphorylation site in RCAN1 by mass spectrometric analysis and revealed that PKA directly phosphorylated RCAN1 at the Ser 93.

Activation of Rac1-dependent redox signaling is critically involved in staurosporine-induced neurite outgrowth in PC12 cells.

Staurosporine, a non-specific protein kinase inhibitor, has been shown to induce neurite outgrowth in PC12 cells, but the mechanism by which staurosporine induces neurite outgrowth is still obscure. In the present study, we investigated whether the activation of Rac1 was responsible for the neurite outgrowth triggered by staurosporine. Staurosporine caused rapid neurite outgrowth independent of the ERK signaling pathways.

CREB-mediated Bcl-2 expression contributes to RCAN1 protection from hydrogen peroxide-induced neuronal death.

Regulator of calcineurin 1 (RCAN1) is located on the Down syndrome critical region (DSCR) locus in human chromosome 21. In this study, we investigated the functional role of RCAN1 in the reactive oxygen species (ROS)-mediated neuronal death signaling. We found that RCAN1 was able to protect the cells from H(2)O(2) -induced cytotoxicity.

Protein kinase A phosphorylates Down syndrome critical region 1 (RCAN1).

The Down syndrome critical region 1 (DSCR1) gene encodes a regulator of the calcineurin 1 (RCAN1) protein, and the elevated levels of RCAN1 are associated with Alzheimer's disease (AD) and Down syndrome (DS). In this report, we found that protein kinase A (PKA) was able to phosphorylate RCAN1 in vitro and in vivo. In addition, we found that the phosphorylation of RCAN1 by PKA caused an increase of RCAN1 expression by increasing of the half-life of the protein.

The regulator of calcineurin 1 (RCAN1/DSCR1) activates the cAMP response element-binding protein (CREB) pathway.

cAMP response element-binding protein (CREB) is one of the best known transcription factors in the development and function of the nervous system. In this report, we found that the regulator of calcineurin 1 (RCAN1), which is overexpressed in the brain of patients with Down syndrome, increased the phosphorylation of CREB and cAMP response element-mediated gene transcription in response to the activation of the intracellular cAMP pathway. Furthermore, we found that the increased activation of CREB signaling by RCAN1 depended on the ability of RCAN1 to inhibit calcineurin activity.

Carmustine induces ERK- and JNK-dependent cell death of neuronally-differentiated PC12 cells via generation of reactive oxygen species.

Accumulation of reactive oxygen species (ROS) caused by the inhibition of glutathione reductase (GR) has been proposed as one of the mechanisms responsible for carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU)-induced cytotoxicity. Since mitogen-activated protein kinases (MAPKs) are known to mediate ROS-dependent cell death in multiple cell types, we examined whether redox-sensitive MAPK activation mediated the carmustine-induced cell death of neuronally differentiated PC12 cells. Carmustine induced a concentration- and time-dependent cell death, which was associated with increased caspase-3 activation, a reduction in GR activity accompanied by a concomitant decrease in reduced glutathione levels, and accumulation of ROS.

Activation of adenylate cyclase by forskolin increases the protein stability of RCAN1 (DSCR1 or Adapt78).

Overexpression of Regulator of Calcineurin 1 (RCAN1/DSCR1/Adapt78) is known to inhibit the calcineurin-NFAT dependent signaling pathway. In this report, we find that activation of adenylate cyclase by forskolin increases the expression of RCAN1 through the increase of the protein's half-life. The ability of forskolin to increase the accumulation of RCAN1 protein is significantly inhibited with protein kinase A inhibitors such as KT5720 and H-89.