Ablation of interleukin-19 improves motor function in a mouse model of amyotrophic lateral sclerosis.

Neuroinflammation by activated microglia and astrocytes plays a critical role in progression of amyotrophic lateral sclerosis (ALS). Interleukin-19 (IL-19) is a negative-feedback regulator that limits pro-inflammatory responses of microglia in an autocrine and paracrine manner, but it remains unclear how IL-19 contributes to ALS pathogenesis. We investigated the role of IL-19 in ALS using transgenic mice carrying human superoxide dismutase 1 with the G93A mutation (SOD1 Tg mice).

Interleukin-19 Abrogates Experimental Autoimmune Encephalomyelitis by Attenuating Antigen-Presenting Cell Activation.

Interleukin-19 (IL-19) acts as a negative-feedback regulator to limit proinflammatory response of macrophages and microglia in autocrine/paracrine manners in various inflammatory diseases. Multiple sclerosis (MS) is a major neuroinflammatory disease in the central nervous system (CNS), but it remains uncertain how IL-19 contributes to MS pathogenesis. Here, we demonstrate that IL-19 deficiency aggravates experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by promoting IL-17-producing helper T cell (Th17 cell) infiltration into the CNS.

Ibudilast attenuates doxorubicin-induced cytotoxicity by suppressing formation of TRPC3 channel and NADPH oxidase 2 protein complexes.

Background And Purpose: Doxorubicin is a highly effective anticancer agent but eventually induces cardiotoxicity associated with increased production of ROS. We previously reported that a pathological protein interaction between TRPC3 channels and NADPH oxidase 2 (Nox2) contributed to doxorubicin-induced cardiac atrophy in mice. Here we have investigated the effects of ibudilast, a drug already approved for clinical use and known to block doxorubicin-induced cytotoxicity, on the TRPC3-Nox2 complex.

Chronic kidney disease after 5/6 nephrectomy disturbs the intestinal microbiota and alters intestinal motility.

Organ-organ crosstalk is involved in homeostasis. Gastrointestinal symptoms are common in patients with renal failure. The aim of this study was to elucidate the relationship between gastrointestinal motility and gastrointestinal symptoms in chronic kidney disease.

The Role of Interleukin-19 in Contact Hypersensitivity.

Interleukin (IL)-19 is a member of the IL-10 family of interleukins and is an immuno-modulatory cytokine produced by the main macrophages. The gastrointestinal tissues of IL-19 knockout mice show exacerbated experimental colitis mediated by the innate immune system and T cells. There is an increasing focus on the interaction and relationship of IL-19 with the function of T cells.

Interleukin-19 is cardioprotective in dominant negative cyclic adenosine monophosphate response-element binding protein-mediated heart failure in a sex-specific manner.

Aim: To investigate the role of interleukin-19 (IL-19) in a murine model of female-dominant heart failure (HF).

Methods: Expression of one copy of a phosphorylation-deficient cyclic adenosine monophosphate response-element binding protein (dnCREB) causes HF, with accelerated morbidity and mortality in female mice compared to males. We assessed expression of IL-19, its receptor isoforms IL-20R α/β, and downstream IL-19 signaling in this model of female-dominant HF.

Aggressive Crosstalk Between Fatty Acids and Inflammation in Macrophages and Their Influence on Metabolic Homeostasis.

From the immunological point of view, macrophages are required to maintain metabolic homeostasis. Recently, there has been an increased focus on the influence of macrophage phenotypes in adipose tissue on the maintenance of metabolic homeostasis in healthy conditions because dysregulated metabolic homeostasis causes metabolic syndrome. This review notes several types of inflammatory and anti-inflammatory mediators in metabolic homeostasis.

Interleukin-19 contributes as a protective factor in experimental Th2-mediated colitis.

Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. IL-19 is a member of the IL-10 family, and IL-10 plays an important role in inflammatory bowel disease. We have previously shown that IL-19 knockout mice are more susceptible to innate-mediated colitis.

Na/Ca exchanger contributes to stool transport in mice with experimental diarrhea.

The Na/Ca exchanger (NCX) is a bidirectional transporter that is controlled by membrane potential and transmembrane gradients of Na and Ca. To reveal the functional role of NCX on gastrointestinal motility, we have previously used NCX1 and NCX2 heterozygote knockout mice (HET). We found that NCX1 and NCX2 play important roles in the motility of the gastric fundus, ileum and distal colon.

Overexpression of Na/Ca exchanger 1 display enhanced relaxation in the gastric fundus.

In gastric smooth muscles, the released Ca activates the contractile proteins and Ca taken up from the cytosol cause relaxation. The Na/Ca exchanger (NCX) is an antiporter membrane protein that controls Ca influx and efflux across the membrane. However, the possible relation of NCX in gastric fundus motility is largely unknown.

Roles of Na(+)/Ca(2+) exchanger isoforms NCX1 and NCX2 in motility in mouse ileum.

The Na(+)/Ca(2+) exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca(2+) concentrations in various tissues. The physiological roles by which NCX influences gastrointestinal motility are incompletely understood, although its role in the heart, brain, and kidney has been widely investigated. In this study, we focused on the functions of the NCX isoforms, NCX1 and NCX2, in the motility of the ileum in the gastrointestinal tract.

Na(+) /Ca(2+) exchanger-heterozygote knockout mice display increased relaxation in gastric fundus and accelerated gastric transit in vivo.

Background: For the contraction and relaxation of gastric smooth muscles to occur, the intracellular Ca(2+) concentration must be increased and decreased, respectively. The Na(+) /Ca(2+) exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca(2+) concentrations.

Methods: To determine the role of NCX in gastrointestinal tissues, we examined electric field stimulation (EFS)-induced relaxations in the circular muscles of the gastric fundus in NCX1 and NCX2 heterozygote knockout mice (HET).

Interleukin 19 reduces inflammation in chemically induced experimental colitis.

Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. Interleukin (IL)-19, a member of the IL-10 family, functions as an anti-inflammatory cytokine. Here, we investigated the contribution of IL-19 to intestinal inflammation in a model of T cell-mediated colitis in mice.

Interleukin-19 acts as a negative autocrine regulator of activated microglia.

Activated microglia can exert either neurotoxic or neuroprotective effects, and they play pivotal roles in the pathogenesis and progression of various neurological diseases. In this study, we used cDNA microarrays to show that interleukin-19 (IL-19), an IL-10 family cytokine, is markedly upregulated in activated microglia. Furthermore, we found that microglia are the only cells in the nervous system that express the IL-19 receptor, a heterodimer of the IL-20Rα and IL-20Rβ subunits.

Na/Ca(2+) exchanger 1 transgenic mice display increased relaxation in the distal colon.

Na(+)/Ca(2+) exchanger 1 (NCX1) is a plasma membrane transporter involved in regulating intracellular Ca(2+) concentrations. NCX1 is critical for Ca(2+) regulation in cardiac muscle, vascular smooth muscle and nerve fibers. However, little is known about the physiological role of NCX1 in gastrointestinal motility.

Evidence that nitric oxide is a non-adrenergic non-cholinergic inhibitory neurotransmitter in the circular muscle of the mouse distal colon: a study on the mechanism of nitric oxide-induced relaxation.

The gastrointestinal tract is composed of outer longitudinal muscle layers and inner circular muscle layers. Nitric oxide (NO), carbon monoxide (CO), and ATP play major roles as non-adrenergic non-cholinergic (NANC) inhibitory neurotransmitters in the longitudinal muscle of the mouse distal colon, whereas it is unclear which NANC inhibitory neurotransmitters are in its circular muscle. We investigated the electric field stimulation (EFS)-induced relaxations in the circular smooth muscle of the distal colon under NANC conditions.

Na⁺/Ca²⁺ exchanger 1/2 double-heterozygote knockout mice display increased nitric oxide component and altered colonic motility.

The Na⁺/Ca²⁺ exchanger (NCX) is a plasma membrane transporter involved in regulating intracellular Ca²⁺ concentrations. NCX is critical for Ca²⁺ regulation in cardiac muscle, vascular smooth muscle, and nerve fibers. To determine the role of NCX1 and NCX2 in gastrointestinal tissues, we examined electric field stimulation (EFS)-induced responses in the longitudinal smooth muscle of the distal colon in NCX1 and NCX2 double-heterozygote knockoutmice (Double HET).

Na(+) /Ca(2+) exchanger 2-heterozygote knockout mice display decreased acetylcholine release and altered colonic motility in vivo.

Background: The Na(+) /Ca(2+) exchanger (NCX) is a plasma membrane transporter involved in regulating intracellular Ca(2+) concentrations. NCX is critical for Ca(2+) regulation in cardiac muscle, vascular smooth muscle, and nerve fibers. However, little is known about the physiological role of NCX in the myenteric neurons and smooth muscles of the gastrointestinal tract.

Clofibrate relaxes the longitudinal smooth muscle of the mouse distal colon through calcium-mediated desensitisation of contractile machinery.

Peroxisome proliferator-activated receptor α (PPAR-α) is a ligand-activated transcription factor that exerts strong effects on metabolic pathways. Our aim was to elucidate the effect of clofibrate, a PPAR-α agonist, on the longitudinal muscle of the mouse distal colon. We initially found that clofibrate induced a relaxation response in this muscle.

Interleukin-19 Is a Negative Regulator of Innate Immunity and Critical for Colonic Protection.

The cytokine, interleukin (IL)-19, is a member of the IL-10 family that includes IL-20, IL-22, IL-24, and IL-26. Recent studies have shown that IL-19 is produced by keratinocytes, epithelial cells, macrophages, and B-cells. Little is known about the exact biological role of IL-19 in immunological regulation, although there is an increasing body of data demonstrating that IL-19 is associated with the development of Th2 responses and the pathogenesis of psoriasis.

Interleukin-19 is a negative regulator of innate immunity and critical for colonic protection.

The cytokine, interleukin (IL)-19, is a member of the IL-10 family that includes IL-20, IL-22, IL-24, and IL-26. Recent studies have shown that IL-19 is produced by keratinocytes, epithelial cells, macrophages, and B-cells. Little is known about the exact biological role of IL-19 in immunological regulation, although there is an increasing body of data demonstrating that IL-19 is associated with the development of Th2 responses and the pathogenesis of psoriasis.

PPARα contributes to colonic protection in mice with DSS-induced colitis.

Inflammatory bowel disease (IBD) is characterized by repeated chronic inflammation of the gastrointestinal tract. We have used the complementary model of colonic inflammation to examine the roles of peroxisome proliferator-activated receptor α (PPARα) in colonic inflammation and thus its possible role in IBD. We characterized an innate immune-mediated model of colitis induced by dextran sulfate sodium (DSS).

Interleukin-19 protects mice from innate-mediated colonic inflammation.

Background: Inflammatory bowel disease (IBD) results from the chronic dysregulation of the mucosal immune system and the aberrant activation of both the innate and the adaptive immune responses. We used two complementary models of colonic inflammation to examine the roles of interleukin (IL)-19 in colonic inflammation and thus its possible role in IBD.

Methods: Using gene-targeting, we generated IL-19-deficient mice.