Background: Cholesteatoma is considered a benign, gradually expanding and destructive epithelial lesion of the temporal bone. The pathogenesis of different classifications of cholesteatoma is marked by similar underlying cellular and molecular processes. Stepwise explanations of the histopathogenesis have been described previously. The current paper focuses on expounding the molecular events ...

BACKGROUND: Mosquitoes respond to infection by mounting immune responses. The primary regulators of these immune responses are cells called hemocytes, which kill pathogens via phagocytosis and via the production of soluble antimicrobial factors. Mosquito hemocytes are circulated throughout the hemocoel (body cavity) by the swift flow of hemolymph (blood), and ...

All common contributing factors to epilepsy such as trauma, malignancies and infections are accompanied by different levels of central nervous system inflammation that in turn have been associated with the occurrence of seizure. Emerging data from human brain tissue and experimental models of epilepsy support the proposed involvement of inflammation ...

ABSTRACT: Rheumatoid arthritis exhibits diurnal variation in symptoms, with patients suffering with increased painful joint stiffness in the early morning. This correlates with an early morning rise in circulating levels of pro-inflammatory cytokines, such as interleukin-6. This temporal variation in disease pathology is directed by the circadian clock, both at ...

The evolution of resistance to parasites has been the focus of numerous theoretical studies and several mechanisms, ranging from innate to acquired immune responses, have been considered. Life-history theory predicts that long-lived species should invest more resources into maintenance and immunity than short-lived species. Here, we provide further theoretical and ...

The redbay ambrosia beetle, Xyleborus glabratus Eichhoff, is an exotic wood-boring insect that vectors the mycopathogen responsible for laurel wilt, a lethal vascular disease of trees in the Lauraceae, including avocado (Persea americana Mill.). Effective semiochemical-based detection and control programs for X. glabratus will require an understanding of the chemical ...

Interleukin-33 is an IL-1 family cytokine that signals via its receptor T1/ST2, and is a key regulator of inflammation, notably the type-2 response implicated in allergic asthma. Critical to our understanding of the role of IL-33 is the identification of the cellular sources of IL-33. Although progress has been made ...

There is ample evidence that immune-related processes in humans are under temporal regulation. The circadian variation of humoral and cellular immunity is well documented and appears to be hormonally modulated via the hypothalamic-pituitary-adrenal axis. In advanced melanoma, it has recently been demonstrated that systemic immunity is repolarized toward a global ...

Persistent neuroinflammation is implicated in the pathogenesis of seizures and neuronal degeneration of temporal lobe epilepsy (TLE). Circulating level of inflammatory cytokines was determined during inter-ictal period of 25 non-operated and 10 patients (OP) submitted to anterior temporal lobectomy. OP patients showed marked reduction of IL-1β, TNFα, MIP-1α, but not ...

Previous studies have linked a reduction in pH in airway, caused by either environmental factors, microaspiration of gastric acid or inflammation, with airway smooth muscle (ASM) contraction and increased airway resistance. Neural mechanisms have been shown to mediate airway contraction in response to reductions in airway pH to < 6.5; ...

Rab7 plays an important role in regulating endocytic traffic. In view of an emerging role of membrane traffic in signaling and diseases, we have examined the possible role of Rab7 in oncogenesis. The role of Rab7 was investigated using shRNA-mediated knockdown in A431 and MCF7 cancer cells. To our surprise, ...

Annexin A2 (p36) is usually present together with its natural ligand p11 as a heterotetramer complex, which has multiple biological functions depending on its cellular localization. However, the detailed mechanism of annexin A2 translocation and its physiological role in inflammation remain unclear. Here, we show that IFN-γ stimulation enhances surface ...

See article in J. Gastroenterol. Hepatol. 2012; 27: 857-861.

The TNF-R1 like receptor Fas is highly expressed on the plasma membrane of hepatocytes and plays an essential role in liver homeostasis. We recently showed that in collagen-cultured primary mouse hepatocytes, Fas stimulation triggers apoptosis via the so-called type I extrinsic signaling pathway. Central to this pathway is the direct ...

The cellular innate immune response is essential for recognizing and defending against viral infection. Retinoic acid-inducible gene-I (RIG-I) and virus-induced signaling adaptor (VISA) mediated immune signalling is critically involved in RNA-virus-induced innate immune responses. Here we demonstrate that the complement C1qA interacts with different RIG-I pathway components and enhances RIG-I-VISA-mediated ...

Loss-of-function mutations in angiogenin (ANG) gene were discovered in amyotrophic lateral sclerosis (ALS) patients and ANG has been shown to prevent neuronal death both in vitro and in vivo. The neuro-protective activity of ANG was brought about partially by inhibiting stress-induced apoptosis. ANG attenuates both the extrinsic and the intrinsic ...

On the one hand, redox emerges as a key mechanism in regulating intra- and intercellular signaling and homeostatic systems. On the other hand, cells of the B lineage provide powerful systems to unravel the intra- and intercellular mechanisms that coordinate the processes of development and terminal differentiation. RECENT ADVANCES: This ...

The recent demonstration of proton signaling in C. elegans muscle contraction suggests a novel mechanism for proton-based intercellular communication and has stimulated enthusiasm for exploring proton signaling in higher organ-isms. Emerging evidence indicates that protons are produced and regulated in localized space and time. Furthermore, identification of proton regulators and ...

Dedifferentiation is a common phenomenon among plants but has only been found rarely in vertebrates where it is mostly associated with regenerative responses such as formation of blastemae in amphibians to initiate replacement of lost body parts. Relatively little attention has been paid to dedifferentiation processes in mammals although a ...

Inflammation is a key physiological response to infection and injury and, although usually beneficial, it can also be damaging to the host. The liver is a prototypical example in this regard because inflammation helps to resolve liver injury, but it also underlies the aetiology of pathologies such as fibrosis and ...

Production of the proinflammatory cytokine interleukin 1β (IL-1β) by dendritic cells is crucial in host defense. Here we identify a previously unknown role for dectin-1 in the activation of a noncanonical caspase-8 inflammasome in response to fungi and mycobacteria. Dectin-1 induced both the production and maturation of IL-1β through signaling ...

Apoptosis in irradiated normal lung tissue has been observed several weeks after radiation. However, the signaling pathway propagating cell death after radiation remains unknown. C57BL/6J mice were irradiated with 15 Gy to the whole thorax. Pro-apoptotic signaling was evaluated 6 weeks after radiation with or without administration of AEOL10150, a ...

Cell death plays an important role in cancer growth and progression, as well as in the efficiency of chemotherapy. Although apoptosis is commonly regarded as the principal mechanism of programmed cell death, it has been increasingly reported that several anti-cancer agents do not only induce apoptosis but other forms of ...

The circulating peptide hormone hepcidin maintains systemic iron homeostasis. Hepcidin production increases during inflammation and as a result of endoplasmic reticulum (ER) stress. Elevated hepcidin levels decrease dietary iron absorption and promote iron sequestration in reticuloendothelial macrophages. Furthermore, increased plasma hepcidin levels cause hypoferremia and the anemia associated with chronic ...

The Toll-like receptor (TLR)/IL-1 receptor (IL-1R) signaling pathway is essential for innate immune responses and immune homeostasis. Lys-63-polyubiquitinated TRAF6 mediates its downstream signaling activation. In a gain-of-expression screen of 66 different deubiquitinating enzymes, we identified USP4 as a potent negative regulator of TLR/IL-1R signaling and TRAF6-interacting protein. USP4 deubiquitinates TRAF6 ...

Progenitor cells (PCs) are key components of vasculogenic remodeling and hematopoietic development. Decreases in the number and function of angiogenic progenitors have been observed in coronary artery disease, hypertension, and diabetic vasculopathy. Several recent studies have also demonstrated a close relationship between increased visceral fat and cardiovascular disease, implying an ...

Inflammasomes are a group of protein complexes built around several proteins, including NLRP3, NLRC4, AIM2 and NLRP6. Recognition of a diverse range of microbial, stress and damage signals by inflammasomes results in direct activation of caspase-1, which subsequently induces secretion of potent pro-inflammatory cytokines and a form of cell death ...

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Its pathogenesis is frequently linked to liver inflammation. Gain-of-function mutations in the gene encoding β-catenin are frequent genetic modifications found in human HCCs. Thus, we investigated whether inflammation was a component of β-catenin-induced tumorigenesis using genetically modified mouse ...

The C-type lectin receptors (CLRs) belong to a large family of proteins that contain a carbohydrate recognition domain (CRD) and calcium binding sites on their extracellular domains. Recent studies indicate that many CLRs, such as Dectin-1, Dectin-2 and Mincle, function as pattern recognition receptors (PRRs) recognizing carbohydrate ligands from infected ...

PURPOSE OF REVIEW: This review highlights new roles of the large family of tripartite motif (TRIM) proteins in antiviral defense. RECENT FINDINGS: Recent research explores the participation of several TRIM family members in regulating the innate immune response. A large number of TRIM genes are upregulated upon treatment by interferon ...

A simultaneous engagement of different pathogen recognition receptors provides a tailor-made adaptive immunity for an efficient defense against distinct pathogens. For example, cross-talk of TLR and C-type lectin signaling effectively shapes distinct gene expression patterns by integrating the signals at the level of NF-κB. In this study, we extend this ...

Inflammation is the principal hallmark of RA. Different pathways are implicated in the production of pro-inflammatory cytokines, the bona fide mediators of this inflammation. Among them are the TNF pathway and the IL-1 receptor/Toll-like receptor (IL-1R/TLR4) pathway. One of the potential negative regulators of IL-1R/TLR4 signalling is the Fas-associated death ...

Matricellular proteins play diverse roles in modulating cell behavior by engaging specific cell surface receptors and interacting with extracellular matrix proteins, secreted enzymes, and growth factors. Studies of such interactions involving thrombospondin-1 have revealed several physiological functions and roles in the pathogenesis of injury responses and cancer, but the relatively ...

Glyceollins, produced to induce disease resistance responses against specific species, such as an incompatible pathogen Phytophthora sojae in soybeans, have the potential to exhibit anti-inflammatory activity in RAW 264.7 cells. To investigate the anti-inflammatory effects of elicited glyceollins via a signaling pathway, we studied the glyceollin signaling pathway using several ...

Niacin and its related derivatives have been shown to have effects on cellular activities. However, the molecular mechanism of its reduced immunosuppressive effects and photoprotective effects remains unclear. In this study, we investigated the molecular mechanism of the photoprotective effect of niacin in ultraviolet (UV)-irradiated human skin keratinocytes (HaCaT cells). ...

Hypoxia is often found in solid tumors and is associated with tumor progression and poor clinical outcomes. The exact mechanisms related to hypoxia-induced invasion and metastasis remain unclear. We elucidated the mechanism by which the nuclear damage associated molecular pattern molecule, high mobility group box 1 (HMGB1), released under hypoxic ...

The transforming growth factor-β (TGF-β) signaling pathway is often misregulated during cancer progression. In early stages of tumorigenesis, TGF-β acts as a tumor suppressor by inhibiting proliferation and inducing apoptosis. However, as the disease progresses, TGF-β switches to promote tumorigenic cell functions, such as epithelial-mesenchymal transition (EMT) and increased cell ...

Oxidised cholesterol metabolites (oxysterols) promote inflammation in a variety of cell types and are thought to be involved in a number of disease pathologies. Oxysterol concentrations are increased in pregnancy, together with systemic oxidative stress and inflammation. We tested the hypothesis that oxysterols 25-hydroxycholesterol (25-OHC) and 7-ketocholesterol (7-ketoC) promote placental ...

Prostaglandin E(2) (PGE(2)) is a lipid mediator that acts by ligating 4 distinct G protein-coupled receptors, E prostanoid (EP) 1 to 4. Previous studies identified the importance of PGE(2) in regulating macrophage functions, but little is known about its effect on macrophage maturation. Macrophage maturation was studied in vitro in ...

Dendritic cells (DCs) bridge innate and adaptive immunity, but how DC-derived signals regulate T cell lineage choices remains unclear. We report here that the mitogen-activated protein kinase p38α programmed DCs to drive the differentiation of the T(H)17 subset of helper T cells. Deletion of p38α in DCs protected mice from ...

The tumor necrosis factor (TNF) superfamily includes death receptor (DR) ligands, such as TNF-α, FasL, and TRAIL. Death receptors (DRs) induce intracellular signaling upon engagement of their cognate DR ligands, either leading to apoptosis, survival, or proinflammatory responses. The DR signaling is mediated by the recruitment of several death domain ...

Mutations of comparative gene identification 58 (CGI-58) in humans cause Chanarin-Dorfman syndrome, a rare autosomal recessive disease in which excess triacylglycerol (TAG) accumulates in multiple tissues. CGI-58 recently has been ascribed two distinct biochemical activities, including coactivation of adipose triglyceride lipase and acylation of lysophosphatidic acid (LPA). It is noteworthy ...

Myocardial necrosis triggers an inflammatory reaction that clears the wound from dead cells and matrix debris, while activating reparative pathways necessary for scar formation. A growing body of evidence suggests that accentuation, prolongation, or expansion of the postinfarction inflammatory response results in worse remodeling and dysfunction following myocardial infarction. This ...

The root of Salvia miltiorrhiza (Salviae miltiorrhizae radix), a herbal medicine has widely been used for the treatment of pain, miscarriage and oedema. In this study, we evaluated the neuroprotective effect of cryptotanshinone (CRT) from Salviae miltiorrhizae radix on sodium-nitroprusside (SNP)-induced apoptosis in neuro-2a (N2a) cells, and further investigated its ...

One of the plausible ways to prevent the reactive oxygen species (ROS)-mediated cellular injury is dietary or pharmaceutical augmentation of endogenous antioxidant defense capacity. In this study, we investigated the neuroprotective effect of fucoidan on H(2)O(2)-induced apoptosis in PC12 cells and the possible signaling pathways involved. The results showed that ...

Inflammatory mediators are operative in the pathogenesis of the most common forms of heart disease. Although in most cases the induction of these pathways is maladaptive and deleterious, there are notable exceptions when inflammatory pathways participate in healing or limiting the extent of injury. The appreciation of the role of ...

The innate immune system responds to endogenous molecules released during cellular stress or those that have undergone modifications normally absent in healthy tissue. These structures are detected by pattern-recognition receptors, alerting the immune system to "danger." In this study, we looked for early signals that direct immune cells to cells ...

TGF-β modulates immune response by suppressing non-regulatory T (Treg) function and promoting Treg function. The question of whether TGF-β achieves distinct effects on non-Treg and Treg cells through discrete signaling pathways remains outstanding. In this study, we investigated the requirements of Smad-dependent and -independent TGF-β signaling for T-cell function. Smad2 ...

Cell-cell communication by juxtacrine signaling plays a key role in the development of the nervous system, from cell fate determination through axonal guidance to synaptogenesis. Interestingly, several juxtacrine signaling systems exhibit an inhibitory interaction between receptors and ligands in the same cell, termed cis inhibition. These include the Notch, semaphorin ...

Interleukin 33 (IL-33), a member of the Interleukin 1 cytokine family, is implicated in numerous human inflammatory diseases such as asthma, atherosclerosis, and rheumatoid arthritis. Despite its pathophysiologic importance, fundamental questions regarding the basic biology of IL-33 remain. Nuclear localization and lack of an export signal sequence are consistent with ...