Multifaceted role of nitric oxide in an in vitro mouse neuronal injury model: transcriptomic profiling defines the temporal recruitment of death signalling cascades.
Journal of Cellular and Molecular Medicine 16(1):41 (2012)
Nitric oxide is implicated in the pathogenesis of various neuropathologies characterized by oxidative stress. Although nitric oxide has been reported to be involved in the exacerbation of oxidative stress observed in several neuropathologies, existent data fail to provide a holistic description ...
Gene profiling reveals hydrogen sulphide recruits death signaling via the N-methyl-D-aspartate receptor identifying commonalities with excitotoxicity.
Journal Of Cellular Physiology 226(5):1308 (2011)
Recently the role of hydrogen sulphide (H(2) S) as a gasotransmitter stimulated wide interest owing to its involvement in Alzheimer's disease and ischemic stroke. Previously we demonstrated the importance of functional ionotropic glutamate receptors (GluRs) by neurons is critical for H(2) S-medi...
The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88.
Nature Immunology 12(4):344 (2011)
Sepsis is one of the most challenging health problems worldwide. Here we found that phagocytes from patients with sepsis had considerable upregulation of Toll-like receptor 4 (TLR4) and TLR2; however, shock-inducing inflammatory responses mediated by these TLRs were inhibited by ES-62, an immuno...
A global transcriptomic view of the multifaceted role of glutathione peroxidase-1 in cerebral ischemic-reperfusion injury.
Free Radical Biology and Medicine 50(6):736 (2011)
Transient cerebral ischemia often results in secondary ischemic/reperfusion injury, the pathogenesis of which remains unclear. This study provides a comprehensive, temporal description of the molecular events contributing to neuronal injury after transient cerebral ischemia. Intraluminal middle ...
New developments on the TNFα-mediated signalling pathways.
Bioscience Reports 31(1):63 (2011)
TNFα (tumour necrosis factor α) is an extensively studied pleiotropic cytokine associated with the pathogenesis of a variety of inflammatory diseases. It elicits a wide spectrum of cellular responses which mediates and regulates inflammation, immune response, cell survival, proliferation and apo...
Up-regulation of endoplasmic reticulum stress-related genes during the early phase of treatment of cultured cortical neurons by the proteasomal inhibitor lactacystin.
Journal Of Cellular Physiology 226(2):494 (2011)
Inhibition of proteasome degradation pathway has been implicated in neuronal cell death leading to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. We and others demonstrated that treatment of cortical neurons with the proteasomal inhibitor lactacystin leads to apo...
Role of sphingosine kinase and sphingosine-1-phosphate in inflammatory arthritis.
World Journal of Biological Chemistry 1(11):321 (2010)
The importance of sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) in inflammation has been extensively demonstrated. As an intracellular second messenger, S1P plays an important role in calcium signaling and mobilization, and cell proliferation and survival. Activation of various pla...
Temporal transcriptomic profiling reveals cellular targets that govern survival in HOCl-mediated neuronal apoptosis.
Life Sciences 87(15-16):457 (2010)
With the identification of hypochlorous acid (HOCl) as a biomarker in diseased brains and endogenous detection of its modified proteins, HOCl might be implicated in the development of neurodegenerative disorders. However, its effect on neuronal cell death has not yet been investigated at gene ex...
Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells.
Journal of Molecular Cell Biology 2(4):199 (2010)
High renewal and maintenance of multipotency of human adult stem cells (hSCs), are a prerequisite for experimental analysis as well as for potential clinical usages. The most widely used strategy for hSC culture and proliferation is using serum. However, serum is poorly defined and has a conside...
SphK1 regulates proinflammatory responses associated with endotoxin and polymicrobial sepsis.
Science 328(5983):1290 (2010)
During sepsis, activation of phagocytes leads to the overproduction of proinflammatory cytokines, causing systemic inflammation. Despite substantial information regarding the underlying molecular mechanisms that lead to sepsis, several elements in the pathway remain to be elucidated. We found th...
Mast cells express IL-17A in rheumatoid arthritis synovium.
Journal of Immunology 184(7):3336 (2010)
The proinflammatory cytokine IL-17A is considered a crucial player in rheumatoid arthritis (RA) pathogenesis. In experimental models of autoimmune arthritis, it has been suggested that the cellular source of IL-17A is CD4(+) T cells (Th17 cells). However, little is known about the source of IL-1...
IL-33 exacerbates autoantibody-induced arthritis.
Journal of Immunology 184(5):2620 (2010)
Rheumatoid arthritis pathogenesis comprises dysregulation in both innate and adaptive immunity. There is therefore intense interest in the factors that integrate these immunologic pathways in rheumatoid arthritis. In this paper, we report that IL-33, a novel member of the IL-1 family, can exacer...
Environmental toxicogenomics: a post-genomic approach to analysing biological responses to environmental toxins.
The International Journal of Biochemistry & Cel... 42(2):230 (2010)
Environmental genomics has revolutionised how researchers can study the molecular basis of adverse effects of environmental toxicants. It is expected that the new discipline will afford efficient and high-throughput means to delineate mechanisms of action, risk assessment, identify and understan...
Substance P in polymicrobial sepsis: molecular fingerprint of lung injury in preprotachykinin-A-/- mice.
Molecular Medicine 16(5-6):188 (2010)
Deletion of mouse preprotachykinin-A (PPTA), which encodes mainly for neuropeptide substance P, has been shown to protect against lung injury and mortality in sepsis. This study explored microarray-based differential gene expression profiles in mouse lung tissue 8 h after inducing microbial seps...
Phospholipase D1 mediates TNFalpha-induced inflammation in a murine model of TNFalpha-induced peritonitis.
PLoS ONE 5(5):e10506 (2010)
Tumor Necrosis Factor alpha (TNFalpha) is a pleiotropic cytokine extensively studied for its role in the pathogenesis of a variety of disease conditions, including in inflammatory diseases. We have recently shown that, in vitro, that TNFalpha utilizes PLD1 to mediate the activation of NFkappaB a...
Resveratrol attenuates C5a-induced inflammatory responses in vitro and in vivo by inhibiting phospholipase D and sphingosine kinase activities.
FASEB Journal 23(8):2412 (2009)
The anti-inflammatory activity of the phytoalexin resveratrol (RSV) was evaluated in C5 anaphylatoxin (C5a)-stimulated primary neutrophils and in a mouse model of acute peritonitis. Pretreatment of human and mouse neutrophils with RSV significantly blocked oxidative burst, leukocyte migration, d...
Distinct roles of sphingosine kinase 1 and 2 in murine collagen-induced arthritis.
Journal of Immunology 183(3):2097 (2009)
Sphingosine kinase (SphK) phosphorylates sphingosine into sphingosine-1-phosphate (S1P). S1P plays a critical role in angiogenesis, inflammation, and various pathologic conditions. To date, two mammalian isoenzymes, SphK1 and SphK2, have been identified. Although both SphK1 and SphK2 share overa...
VAMP8 is essential in anaphylatoxin-induced degranulation, TNF-alpha secretion, peritonitis, and systemic inflammation.
Journal of Immunology 183(2):1413 (2009)
VAMP8, a member of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) family of fusion proteins, initially characterized in endosomal and endosomal-lysosomal fusion, may also function in regulated exocytosis. VAMP8 physiological function in inflammation has...
Differential signal transduction, membrane trafficking, and immune effector functions mediated by FcgammaRI versus FcgammaRIIa.
Blood 114(2):318 (2009)
Receptors for the fragment crystallizable region of immunoglobulin-G (FcgammaRs) play an important role in linking the humoral and cellular arms of the immune response. In this study, we present a comprehensive functional comparison of 2 human Fc-receptors, FcgammaRI and FcgammaRIIa. Activation ...
Sphingosine kinase 1 is pivotal for Fc epsilon RI-mediated mast cell signaling and functional responses in vitro and in vivo.
Journal of Immunology 183(1):221 (2009)
Mast cell degranulation is pivotal to allergic diseases; investigating novel pathways triggering mast cell degranulation would undoubtedly have important therapeutic potential. FcepsilonRI-mediated degranulation has contradictorily been shown to require SphK1 or SphK2, depending on the reports. ...