Inactivation of Mycobacteria by Radicals from Non-Thermal Plasma Jet.

Mycobacterial cell walls comprise thick and diverse lipids and glycolipids that act as a permeability barrier to antibiotics or other chemical agents. The use of OH radicals from a non-thermal plasma jet (NTPJ) for the inactivation of mycobacteria in aqueous solution was adopted as a novel approach. Addition of water vapor in a nitrogen plasma jet generated OH radicals, which converted to hydrogen peroxide (HO) that inactivated non-pathogenic and pathogenic H37Rv.

SIRT3 promotes antimycobacterial defenses by coordinating mitochondrial and autophagic functions.

SIRT3 (sirtuin 3), a mitochondrial protein deacetylase, maintains respiratory function, but its role in the regulation of innate immune defense is largely unknown. Herein, we show that SIRT3 coordinates mitochondrial function and macroautophagy/autophagy activation to promote anti-mycobacterial responses through PPARA (peroxisome proliferator activated receptor alpha). SIRT3 deficiency enhanced inflammatory responses and mitochondrial dysfunction, leading to defective host defense and pathological inflammation during mycobacterial infection.

Mitochondrial Control of Innate Immunity and Inflammation.

Mitochondria are key organelles involved in energy production, functioning as the metabolic hubs of cells. Recent findings emphasize the emerging role of the mitochondrion as a key intracellular signaling platform regulating innate immune and inflammatory responses. Several mitochondrial proteins and mitochondrial reactive oxygen species have emerged as central players orchestrating the innate immune responses to pathogens and damaging ligands.

Negative regulators and their mechanisms in NLRP3 inflammasome activation and signaling.

Inflammasomes are cytosolic multiprotein complexes that cause the release of biologically active interleukin-1β. The best-characterized inflammasome is the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 or Nod-like receptor protein 3) inflammasome. The NLRP3 inflammasome forms an assembly consisting of the ASC (apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain) adaptor protein and the effector, caspase-1 (cysteine-dependent aspartate-directed protease-1).

New Insights into Vitamin D and Autophagy in Inflammatory Bowel Diseases.

Vitamin D exerts an anti-inflammatory effect in both health and disease. The importance of vitamin D in protection against various inflammatory and metabolic diseases, including inflammatory bowel diseases (IBDs), has been discussed. Considerable data indicate a role for vitamin D in the activation of autophagy, an intracellular renewal system that maintains homeostasis by eliminating large protein aggregates and damaged organelles.

MIR144* inhibits antimicrobial responses against Mycobacterium tuberculosis in human monocytes and macrophages by targeting the autophagy protein DRAM2.

Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized.

The structural basis for the negative regulation of thioredoxin by thioredoxin-interacting protein.

The redox-dependent inhibition of thioredoxin (TRX) by thioredoxin-interacting protein (TXNIP) plays a pivotal role in various cancers and metabolic syndromes. However, the molecular mechanism of this regulation is largely unknown. Here, we present the crystal structure of the TRX-TXNIP complex and demonstrate that the inhibition of TRX by TXNIP is mediated by an intermolecular disulphide interaction resulting from a novel disulphide bond-switching mechanism.

TXNIP deficiency exacerbates endotoxic shock via the induction of excessive nitric oxide synthesis.

Thioredoxin-interacting protein (TXNIP) has multiple functions, including tumor suppression and involvement in cell proliferation and apoptosis. However, its role in the inflammatory process remains unclear. In this report, we demonstrate that Txnip⁻/⁻ mice are significantly more susceptible to lipopolysaccharide (LPS)-induced endotoxic shock.

TXNIP interacts with hEcd to increase p53 stability and activity.

The p53 protein plays a central role in cell cycle arrest and apoptosis in response to diverse stress stimuli. Human ecdysoneless (hEcd) is known for its role in stabilizing the p53 protein level and increasing p53-mediated transcription. Here, we report that thioredoxin interacting protein (TXNIP), a member of the tumor suppressor family, interacts with hEcd and decreases MDM2-mediated p53 ubiquitination, leading to p53 stabilization and an increase in p53 activity.

TXNIP maintains the hematopoietic cell pool by switching the function of p53 under oxidative stress.

Reactive oxygen species (ROS) are critical determinants of the fate of hematopoietic stem cells (HSCs) and hematopoiesis. Thioredoxin-interacting protein (TXNIP), which is induced by oxidative stress, is a known regulator of intracellular ROS. Txnip(-/-) old mice exhibited elevated ROS levels in hematopoietic cells and showed a reduction in hematopoietic cell population.

VDUP1 exacerbates bacteremic shock in mice infected with Pseudomonas aeruginosa.

Vitamin-D3 upregulated protein-1 (VDUP1) is a stress response protein. Pseudomonas aeruginosa (P. aeruginosa) infection is a leading cause of death.

Vitamin D3 upregulated protein 1 suppresses TNF-α-induced NF-κB activation in hepatocarcinogenesis.

Vitamin D(3) upregulated protein 1 (VDUP1) is a candidate tumor suppressor, the expression of which is dramatically reduced in various tumor tissues. In this study, we found that VDUP1 expression is suppressed during human hepatic carcinogenesis, and mice lacking VDUP1 are much more susceptible to diethylnitrosamine-induced hepatocarcinogenesis compared with wild type mice. VDUP1-deficient tumors proliferated significantly more than wild type tumors and had corresponding changes in the expression of key cell cycle regulatory proteins.

TXNIP regulates germinal center generation by suppressing BCL-6 expression.

The detailed mechanism driving the germinal center (GC) reaction to B cell lymphomagenesis has not been clarified. Thioredoxin interacting protein (TXNIP), also known as vitamin D3 up-regulated protein 1 which is an important tumor repressor, is involved in stress responses, redox regulation, and cellular proliferation. Here, we report that TXNIP has a potential role in the formation of GC in peripheral lymphoid organs where B lymphocytes divide rapidly.

YC-1 enhances natural killer cell differentiation from hematopoietic stem cells.

NK cells play crucial roles in innate immunity and adaptive immunity. The detailed mechanisms, however, governing NK cell development remains unclear. In this study, we report that YC-1 significantly enhances NK cell populations differentiated from human umbilical cord blood hematopoietic stem cells (HSCs).

VDUP1 mediates nuclear export of HIF1alpha via CRM1-dependent pathway.

Hypoxia-inducible factor 1alpha (HIF1alpha) is a critical transcriptional factor for inducing tumor metastasis, and stabilized under hypoxia but degraded by von Hippel-Lindau protein (pVHL) under normoxia. For the maximal degradation of HIF1alpha, it must be exported to the cytoplasm via an unidentified transporter. Here, we demonstrate that vitamin D3 up-regulated protein 1 (VDUP1) associates with the beta-domain of pVHL and enhances the interaction between pVHL and HIF1alpha to promote the nuclear export and degradation of HIF1alpha hypoxia-independently.

Hypoxia-induced IL-18 increases hypoxia-inducible factor-1alpha expression through a Rac1-dependent NF-kappaB pathway.

Interleukin-18 (IL-18) plays pivotal roles in linking inflammatory immune responses and tumor progression and metastasis, yet the manner in which this occurs remains to be sufficiently clarified. Here we report that hypoxia induces the transcription and secretion of IL-18, which subsequently induces the expression of hypoxia-inducible factor-1alpha (HIF-1alpha). Mechanistically, IL-18 induces HIF-1alpha through the activity of the GTPase Rac1, which inducibly associates with the IL-18 receptor beta (IL-18Rbeta) subunit, via a PI3K-AKT-NF-kappaB-dependent pathway.

Diverse functions of VDUP1 in cell proliferation, differentiation, and diseases.

Vitamin D3 up-regulated protein 1 (VDUP1) is a multifunctional protein involved in maintaining cellular homeostasis. VDUP1 is induced by a variety of stresses. Inversely, VDUP1 is often reduced in various tumor tissues and cell lines.

Curcumin attenuates glutamate-induced HT22 cell death by suppressing MAP kinase signaling.

Glutamate induces cell death by upsetting the cellular redox homeostasis, termed oxidative glutamate toxicity, in a mouse hippocampal cell line, HT22. Extracellular signal-regulated kinases (ERK) 1/2 are known key players in this process. Here we characterized the roles of both MAP kinases and cell cycle regulators in mediating oxidative glutamate toxicity and the neuroprotective mechanisms of curcumin in HT22 cells.