IL-25 Orchestrates Activation of Th Cells via Conventional Dendritic Cells in Tissue to Exacerbate Chronic House Dust Mite-Induced Asthma Pathology.

House dust mite (HDM) extract is a common trigger of asthma in humans. Chronic exposure to HDM also induces asthma-like pathology in mice. Allergic responses to HDM and other allergens are linked to release of IL-25, IL-33, and TSLP by epithelial cells; these cytokines, especially IL-33, target innate lymphoid cells type 2 to produce type 2 cytokines.

IL-20-Receptor Signaling Delimits IL-17 Production in Psoriatic Inflammation.

IL-17 cytokines, in particular IL-17A, are critical effectors in psoriasis. Antibodies that block IL-17A are highly efficacious in treating psoriasis. Likewise, disruption of IL-17 cytokines signaling, such as via the loss of the adaptor CIKS/Act1, ameliorates inflammation in mouse models of psoriasis.

IGF-II induced by hepatitis B virus X protein regulates EMT via SUMO mediated loss of E-cadherin in mice.

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer mortality. Prognosis of this disease largely depends on its stage. An Enlarged liver, due to dysplasia, may be a critical point in the multi-step progression to HCC.

Cutting Edge: IL-25 Targets Dendritic Cells To Attract IL-9-Producing T Cells in Acute Allergic Lung Inflammation.

Asthma is a common inflammatory disease of airways that is often associated with type 2 responses triggered by allergens, such as house dust mites (HDMs). IL-25 is a key mucosal cytokine that may be produced by stressed epithelial cells; it rapidly activates type 2 innate lymphoid cells to produce IL-13 and IL-5. When administered directly into lungs, IL-25 induces acute inflammation.

Adaptive immune-mediated host resistance to Toxoplasma gondii is governed by the NF-κB regulator Bcl-3 in dendritic cells.

The atypical IκB family member Bcl-3 associates with p50/NF-κB1 or p52/NF-κB2 homodimers in nuclei, thereby either positively or negatively modulating transcription in a context-dependent manner. Previously we reported that Bcl-3 was critical for host resistance to Toxoplasma gondii. Bcl-3-deficient mice succumbed within 3-5 weeks after infection, correlating with an apparently impaired Th1-type adaptive immune response.

The NF-κB regulator Bcl-3 modulates inflammation during contact hypersensitivity reactions in radioresistant cells.

Bcl-3 is an atypical member of the IκB family. Bcl-3 functions as a cofactor of p50/NF-κB1 or p52/NF-κB2 homodimers in nuclei, where it modulates NF-κB-regulated transcription in a context-dependent way. Bcl-3 has tumorigenic potential, is critical in host defense of pathogens, and has been reported to ameliorate or exacerbate inflammation, depending on disease model.

The oncoprotein and transcriptional regulator Bcl-3 governs plasticity and pathogenicity of autoimmune T cells.

Bcl-3 is an atypical member of the IκB family that modulates transcription in the nucleus via association with p50 (NF-κB1) or p52 (NF-κB2) homodimers. Despite evidence attesting to the overall physiologic importance of Bcl-3, little is known about its cell-specific functions or mechanisms. Here we demonstrate a T-cell-intrinsic function of Bcl-3 in autoimmunity.

The NF-κB regulator Bcl-3 governs dendritic cell antigen presentation functions in adaptive immunity.

Bcl-3 is an atypical member of the IκB family and modulates gene expression via interaction with p50/NF-κB1 or p52/NF-κB2 homodimers. We report in the present study that Bcl-3 is required in dendritic cells (DCs) to assure effective priming of CD4 and CD8 T cells. Lack of Bcl-3 in bone marrow-derived DCs blunted their ability to expand and promote effector functions of T cells upon Ag/adjuvant challenge in vitro and after adoptive transfers in vivo.

IL-17 drives psoriatic inflammation via distinct, target cell-specific mechanisms.

Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and differentiation and by an influx of inflammatory cells. The mechanisms underlying psoriasis in humans and in mouse models are poorly understood, although evidence strongly points to crucial contributions of IL-17 cytokines, which signal via the obligatory adaptor CIKS/Act1. Here we identify critical roles of CIKS/Act1-mediated signaling in imiquimod-induced psoriatic inflammation, a mouse model that shares features with the human disease.

Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis.

Aim: To investigate the effect of methylsulfonylmethane (MSM), recently reported to have anti-cancer effects, in liver cancer cells and transgenic mice.

Methods: Three liver cancer cell lines, HepG2, Huh7-Mock and Huh7-H-ras (G12V), were used. Cell growth was measured by Cell Counting Kit-8 and soft agar assay.

Interleukin-17 cytokines are critical in development of fatal lupus glomerulonephritis.

Systemic lupus erythematosus is a potentially fatal autoimmune disease. Although interleukin-17 (IL-17) has been linked to human lupus and mouse models of this disease, it has not been addressed whether this cytokine plays a critical role in fatal lupus pathology. Here we have demonstrated that increased production of IL-17 cytokines and their signaling via the adaptor protein CIKS (a.

Peroxiredoxin I deficiency attenuates phagocytic capacity of macrophage in clearance of the red blood cells damaged by oxidative stress.

The role of peroxiredoxin (Prx) I as an erythrocyte antioxidant defense in red blood cells (RBCs) is controversial. Here we investigated the function of Prx I by using Prx I(-/-) and Prx I/II(-/-) mice. Prx I(-/-) mice exhibited a normal blood profile.

Peroxiredoxin II is essential for preventing hemolytic anemia from oxidative stress through maintaining hemoglobin stability.

The pathophysiology of oxidative hemolytic anemia is closely associated with hemoglobin (Hb) stability; however, the mechanism of how Hb maintains its stability under oxidative stress conditions of red blood cells (RBCs) carrying high levels of oxygen is unknown. Here, we investigated the potential role of peroxiredoxin II (Prx II) in preventing Hb aggregation induced by reactive oxygen species (ROS) using Prx II knockout mice and RBCs of patients with hemolytic anemia. Upon oxidative stress, ROS and Heinz body formation were significantly increased in Prx II knockout RBCs compared to wild-type (WT), which ultimately accelerated the accumulation of hemosiderin and heme-oxygenase 1 in the Prx II knock-out livers.

Reactive oxygen species mediated DNA damage is essential for abnormal erythropoiesis in peroxiredoxin II(-/-) mice.

Erythroid cells are highly prone to oxidative damage generated during erythropoiesis and thus are well equipped with antioxidant defense systems. However, their roles have been poorly characterized. Here, we investigated the role of peroxiredoxin II in mouse erythropoiesis.

CIKS/Act1-mediated signaling by IL-17 cytokines in context: implications for how a CIKS gene variant may predispose to psoriasis.

Psoriasis is a relapsing skin disease characterized by abnormal keratinocyte proliferation and differentiation and by an influx of inflammatory immune cells. Recently, IL-17 cytokines have been strongly implicated as critical for the pathogenesis of this disease. IL-17A (also known as IL-17) and IL-17F are the signature cytokines of Th17 cells, but are also produced by innate cells, including γδ T cells present in skin, whereas epithelial cells, including keratinocytes, may produce IL-17C.

Chemopreventive effect of Curcuma longa Linn on liver pathology in HBx transgenic mice.

Unlike other forms of hepatocellular carcinoma (HCC), HCC induced by hepatitis B virus (HBV) infection shows a poor prognosis after conventional therapies. HBV induces liver cirrhosis and HCC. Many researchers have made efforts to find new substances that suppress the activity of HBV.

Oxidative stress and antioxidants in hepatic pathogenesis.

Long term hepatitis B virus (HBV) infection is a major risk factor in pathogenesis of chronic liver diseases, including hepatocellular carcinoma (HCC). The HBV encoded proteins, hepatitis B virus X protein and preS, appear to contribute importantly to the pathogenesis of HCC. Both are associated with oxidative stress, which can damage cellular molecules like lipids, proteins, and DNA during chronic infection.

HBx-induced reactive oxygen species activates hepatocellular carcinogenesis via dysregulation of PTEN/Akt pathway.

Aim: To investigate the role of hepatitis B virus X-protein (HBx)-induced reactive oxygen species (ROS) on liver carcinogenesis in HBx transgenic mice and HepG2-HBx cells.

Methods: Cell growth rate was analyzed, and through western blotting, mitogenic signaling was observed. Endogenous ROS from wild and HBx transgenic mice and HepG2-Mock and HBx cells were assayed by FACScalibur.

2'-Benzoyloxycinnamaldehyde inhibits tumor growth in H-ras12V transgenic mice via downregulation of metallothionein.

Cinnamaldehydes have been reported to induce apoptosis in human carcinomas through the generation of reactive oxygen species (ROS). 2'-benzoyloxycinnamaldehyde (BCA) has been reported to inhibit tumor formation in H-ras12V transgenic mice. To see the antitumor effects of BCA, BCA was administrated intraperitoneally (50 mg/kg) to H-ras12V transgenic mice for 3 wk, and it was found that the hepatic tumor volume and the total number of tumors were decreased in BCA-treated mice as compared to control H-ras12V transgenic mice.

Non-structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic mice.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). However, the mechanism of HCV pathogenesis is not well understood. Our previous in vitro studies suggested that non-structural 5A (NS5A) protein may play an important role in liver pathogenesis.