Glutamine deficiency shifts the asthmatic state toward neutrophilic airway inflammation.

Background: The administration of L-glutamine (Gln) suppresses allergic airway inflammation via the rapid upregulation of MAPK phosphatase (MKP)-1, which functions as a negative regulator of inflammation by deactivating p38 and JNK mitogen-activated protein kinases (MAPKs). However, the role of endogenous Gln remains to be elucidated. Therefore, we investigated the mechanism by which endogenous Gln regulates MKP-1 induction and allergic airway inflammation in an ovalbumin-based murine asthma model.

GPCR Kinase (GRK)-2 Is a Key Negative Regulator of Itch: l-Glutamine Attenuates Itch via a Rapid Induction of GRK2 in an ERK-Dependent Way.

Many itch mediators activate GPCR and trigger itch via activation of GPCR-mediated signaling pathways. GPCRs are desensitized by GPCR kinases (GRKs). The aim of this study is to explore the role of GRKs in itch response and the link between GRKs and glutamine, an amino acid previously shown to be an itch reliever.

l-Glutamine Attenuates DSS-Induced Colitis via Induction of MAPK Phosphatase-1.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a multifactorial inflammatory disease of the small intestine and colon. Many investigators have reported that l-glutamine (Gln) therapy improves outcomes of experimental colitis models, although the mechanism is not fully understood. Regarding the anti-inflammatory properties of Gln, we have shown that Gln can effectively deactivate cytosolic phospholipase A₂ (cPLA₂) by rapid induction of MAPK phosphatase (MKP)-1.

FcγR/ROS/CK2α Is the Key Inducer of NF-κB Activation in a Murine Model of Asthma.

Background: The transcription factor nuclear factor (NF)-κB plays a pivotal role in the development of allergic airway inflammation. However, the mechanism of NF-κB activation in asthma remains to be elucidated.

Methods: CK2α activation was assessed by CK2α phosphorylation and protein expression.

The extracellular matrix protein Edil3 stimulates osteoblast differentiation through the integrin α5β1/ERK/Runx2 pathway.

Epidermal growth factor-like repeats and discoidin I-like domain 3 (Edil3) is an extracellular matrix protein containing an Arg-Gly-Asp (RGD) motif that binds integrin. Recently, Edil3 has been implicated in various biological processes, including angiogenesis and cellular differentiation. It can inhibit inflammatory bone destruction.

Glutamine Prevents Late-Phase Anaphylaxis via MAPK Phosphatase 1-Dependent Cytosolic Phospholipase A2 Deactivation.

Background: Cytosolic phospholipase A2 (cPLA2) plays a key role in the development of late-phase anaphylaxis. L-Glutamine (Gln), a nonessential amino acid, has anti-inflammatory activity via inhibiting cPLA2.

Methods: We used a penicillin-induced murine model of anaphylaxis, and late-phase anaphylaxis was quantified by measuring the increase in the hematocrit (Ht) value.

Glutamine up-regulates MAPK phosphatase-1 induction via activation of Ca→ ERK cascade pathway.

The non-essential amino acid L-glutamine (Gln) displays potent anti-inflammatory activity by deactivating p38 mitogen activating protein kinase and cytosolic phospholipase A via induction of MAPK phosphatase-1 (MKP-1) in an extracellular signal-regulated kinase (ERK)-dependent way. In this study, the mechanism of Gln-mediated ERK-dependency in MKP-1 induction was investigated. Gln increased ERK phosphorylation and activity, and phosphorylations of Ras, c-Raf, and MEK, located in the upstream pathway of ERK, in response to lipopolysaccharide and .

Platelet-activating factor enhances tumour metastasis via the reactive oxygen species-dependent protein kinase casein kinase 2-mediated nuclear factor-κB activation.

Platelet-activating factor (PAF) promotes tumour metastasis via activation of the transcription factor nuclear factor-κB (NF-κB). We here investigated the role of the protein kinase CK2 (formerly Casein Kinase 2 or II) in PAF-induced NF-κB activation and tumour metastasis, given that PAF has been reported to increase CK2 activity, and that CK2 plays a key role in NF-κB activation. PAF increased CK2 activity, phosphorylation and protein expression in vivo as well as in vitro.

Cholera toxin breakdowns oral tolerance via activation of canonical NF-κB.

The mechanisms of mucosal immunogenicity and adjuvanticity of bacterial exotoxins remains unknown. In this study, we investigated the role of the transcription factor nuclear factor-κB (NF-κB) in cholera toxin (CT)-induced alteration of oral tolerance. Feeding CT abrogated ovalbumin (OVA)-induced oral tolerance, as evaluated by OVA-specific serum antibody responses, and CD4(+) T cell proliferation.

PTEN/MAPK pathways play a key role in platelet-activating factor-induced experimental pulmonary tumor metastasis.

In this study, we investigated the role of PTEN (phosphatase and tensin homolog deleted on chromosome 10) in a platelet-activating factor (PAF)-induced experimental pulmonary tumor metastasis model. An adenovirus carrying PTEN cDNA (Ad-PTEN) reversed PAF-induced increase in phosphorylation of AKT as well as pulmonary metastasis of B16F10. PAF-induced pulmonary metastasis was inhibited by MAPK inhibitors, but not by PI3K inhibitor.

Glutamine suppresses airway neutrophilia by blocking cytosolic phospholipase A(2) via an induction of MAPK phosphatase-1.

Neutrophils are inflammatory cells that may contribute in a crucial way to the pathophysiology of steroid-resistant severe asthma. We previously reported that the nonessential amino acid l-glutamine (Gln) suppressed the recruitment of neutrophils into the airway in a murine model of asthma. In this study, we investigated the mechanisms by which Gln exerts beneficial effects in airway neutrophilia.

Glutamine suppresses DNFB-induced contact dermatitis by deactivating p38 mitogen-activated protein kinase via induction of MAPK phosphatase-1.

L-glutamine (Gln) is a nonessential amino acid that is the most abundant amino acid in plasma. Gln has been reported to have an anti-inflammatory activity that involves deactivation of mitogen-activated protein kinases (MAPKs) in a MAPK phosphatase (MKP)-1-dependent manner. This study investigated the role of Gln in the inhibition of DNFB-induced allergic contact dermatitis (CD) in the ears of mice, and specifically the involvement of Gln in p38 MAPK inhibition.

Glutamine suppresses dinitrophenol fluorobenzene-induced allergic contact dermatitis and itching: inhibition of contact dermatitis by glutamine.

Background: Cytoplasmic phospholipase A(2) (cPLA(2)) is importantly implicated in a variety of inflammatory diseases by liberating arachidonic acid from phospholipids. The increased cPLA(2) activities as well as increased levels of cPLA(2) metabolites are associated with pathogenesis of many inflammatory skin disorders including atopic dermatitis. The non-essential amino acid l-glutamine (Gln) has been reported to have an anti-inflammatory activity.

Glutamine inhibits platelet-activating factor-mediated pulmonary tumour metastasis.

Inflammation has been increasingly recognised as an important component of tumourigenesis. Platelet-activating factor (PAF), a potent inflammatory mediator, has the ability to enhance tumour growth and metastasis. In this study, we have investigated (i) the role of mitogen-activated protein kinases (MAPKs) and (ii) the therapeutic efficacy of the non-essential amino acid, l-glutamine (Gln), which evidences MAPKs inhibition activity in PAF-mediated B16F10 melanoma metastasis to the lungs.

IgG immune complex induces the recruitment of inflammatory cells into the airway and TNF-mediated late airway hyperresponsiveness via NF-κB activation in mice.

Background: Many of the inflammatory proteins that are expressed in asthmatic airways are regulated, at least partially, by nuclear factor (NF)-κB. Blockade of NF-κB activity has resulted in attenuation of the cardinal features of asthma. Thus, delineating the mechanisms involved in NF-κB activation in asthma might provide an interesting approach to improving the management of asthma.

Protein kinase CK2/PTEN pathway plays a key role in platelet-activating factor-mediated murine anaphylactic shock.

Platelet-activating factor (PAF) is a major mediator in the induction of fatal hypovolemic shock in murine anaphylaxis. This PAF-mediated effect has been reported to be associated with PI3K/Akt-dependent eNOS-derived NO. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is phosphatidylinositol phosphate phosphatase, which negatively controls PI3K by dephosphorylating the signaling lipid, phosphatidylinositol 3,4,5-triphosphate.

Mechanisms of platelet-activating factor-induced enhancement of VEGF expression.

It has been previously reported that platelet-activating factor (PAF) induces the expression of vascular endothelial growth factor (VEGF) via the downregulation of p53 activity. In this study, we attempted to characterize the mechanism by which p53 activity negatively regulates PAF-induced VEGF expression. PAF increased luciferase activity as well as VEGF mRNA expression in human non-small cell lung cancer cell line H1299 transfected with VEGF luciferase reporter plasmid (VEGF-Luc).

Cytoplasmic phospholipase A2 metabolites play a critical role in pulmonary tumor metastasis in mice.

Background: Cytoplasmic PLA(2) (cPLA2) has been shown to be the major enzyme responsible for arachidonic acid (AA) release. Because of this key role of cPLA(2) in AA production, cPLA(2) involvement in tumorigenesis has been suggested. However, contradictory data are found in the literature.

Glutamine protects mice from lethal endotoxic shock via a rapid induction of MAPK phosphatase-1.

The nonessential amino acid L-glutamine (Gln) is the most abundant amino acid in plasma. Clinical trials have demonstrated that Gln therapy is safe and improves clinical outcomes in critically ill patients. We have previously shown that Gln protect animals from endotoxic shock through the inhibition of cytosolic phospholipase A(2) activity.

CpG-ODN-based immunotherapy is effective in controlling the growth of metastasized tumor cells.

Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpG-ODN) act as potent immune stimulators by activating innate immunity through toll-like receptor 9. These immunomodulatory effects of CpG-ODN have been reported to be associated with anti-tumor immunity. In this study, we used a murine B16F10 melanoma model and a CT26 colon cancer model to assess whether CpG-ODN-based immunotherapy was effective in inhibiting tumor cells that have already metastasized to distant organs.

Simultaneous degradation of phytic acid and starch by an industrial strain of Saccharomyces cerevisiae producing phytase and alpha-amylase.

Phytase liberates inorganic phosphate from phytic acid (myo-inositol hexakisphosphate) which is the major phosphate reserve in plant-derived foods and feeds. An industrial strain of Saccharomyces cerevisiae expressing the Debaryomyces castellii phytase gene (phytDc) and D. occidentalis alpha-amylase gene (AMY) was developed.

Tumor necrosis factor-alpha develops late anaphylactic reaction through cytosolic phospholipase A(2) activation.

Background: We have recently reported that tumor necrosis factor (TNF)-alpha plays an important role in the development of a late anaphylactic reaction, but the downstream pathway beyond TNF-alpha remains unclear.

Objective: It was the aim of this study to examine whether TNF-alpha induces late-phase anaphylaxis via the activation of cytosolic phospholipase A(2) (cPLA(2)).

Methods: Using a murine model of active systemic anaphylaxis to penicillin V, the induction of the late phase of anaphylaxis was quantified by measuring the increase in hematocrit value as well as the plasma level of platelet-activating factor in TNF-alpha knockout mice.

Downregulation by lipopolysaccharide of Notch signaling, via nitric oxide.

The Notch signaling pathway appears to perform an important function in inflammation. Here, we present evidence to suggest that lipopolysaccharide (LPS) suppresses Notch signaling via the direct modification of Notch by the nitration of tyrosine residues in macrophages. In the RAW264.

Nitric oxide plays a key role in the platelet-activating factor-induced enhancement of resistance against systemic candidiasis.

Platelet-activating factor (PAF) has been demonstrated to augment resistance against Candida albicans infection. In this study, the role of nitric oxide (NO) in PAF-induced resistance in the kidneys was investigated. Pretreatment of the C.

CpG oligodeoxynucleotides protect mice from lethal challenge with Candida albicans via a pathway involving tumor necrosis factor-alpha-dependent interleukin-12 induction.

In this study, we have attempted to determine whether the systemic administration of CpG oligodeoxynucleotide (CpG-ODN) 1826 would protect mice against systemic lethal Candida albicans infection. CpG-ODNs were found completely to protect mice from death and also reduced the growth of C. albicans in the kidneys.