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A. Dean Befus

Bio: A. Dean Befus is an academic researcher from University of Alberta. The author has contributed to research in topics: Mast cell & Inflammation. The author has an hindex of 34, co-authored 103 publications receiving 3645 citations. Previous affiliations of A. Dean Befus include Alberta Health Services & Shanghai Jiao Tong University.


Papers
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Journal ArticleDOI
TL;DR: This review summarizes the knowledge of MC mediators and will focus on what is known about the discriminatory release of these mediators dependent upon diverse stimuli, MC phenotypes, and species of origin, as well as on the intracellular synthesis, storage, and secretory processes involved.
Abstract: Mast cells (MC) are widely distributed throughout the body and are common at mucosal surfaces, a major host-environment interface. MC are functionally and phenotypically heterogeneous depending on the microenvironment in which they mature. Although MC have been classically viewed as effector cells of IgE-mediated allergic diseases, they are also recognized as important in host defense, innate and acquired immunity, homeostatic responses, and immunoregulation. MC activation can induce release of preformed mediators such as histamine from their granules, as well as release of de novo synthesized lipid mediators, cytokines and chemokines that play diverse roles, not only in allergic reactions but also in numerous physiological and pathophysiological responses. Indeed, MC release their mediators in a discriminating and chronological manner, depending upon the stimuli involved and their signaling cascades (e.g., IgE-mediated or Toll Like Receptor-mediated). However, the precise mechanisms underlying differential mediator release in response to these stimuli are poorly known. This review summarizes our knowledge of MC mediators and will focus on what is known about the discriminatory release of these mediators dependent upon diverse stimuli, MC phenotypes and species of origin, as well as on the intracellular synthesis, storage and secretory processes involved.

293 citations

Journal ArticleDOI
TL;DR: A group of compounds other than doxantrazole are identified, which inhibit histamine secretion by MMC, and all compounds with the possible exception of taxifolin demonstrate significant activity against rat PMC.
Abstract: Quercetin, a naturally occurring flavonol structurally related to the antiallergic drug disodium cromoglycate inhibits anaphylactic histamine release from MMC isolated from the small bowel LP of the rat previously infected with the nematode Nippostrongylus brasiliensis. This contrasts with our previous observation that cromoglycate is inactive in this system. The present effect is immediate and does not decrease on preincubation with the drug. The flavonoids acacetin , apigenin , chrysin , and phloretin also demonstrate significant activity but are less potent than quercetin. Catechin, flavone, morin, and taxifolin are inactive. These results resemble those previously reported for the human basophil. In contrast, all compounds with the possible exception of taxifolin demonstrate significant activity against rat PMC. Acacetin and chrysin are the most effective inhibitors and are more active than quercetin. Rutin (the glycane of quercetin) and phlorezin (the glycane of phloretin) are inactive in both systems. These results are discussed in terms of the functional heterogeneity of mast cells from different sources and identify a group of compounds other than doxantrazole (reported previously), which inhibit histamine secretion by MMC.

234 citations

Journal ArticleDOI
TL;DR: Par-2 receptors appear to play an important role in the regulation of MMP-9 release from airway epithelial cells, and may be critical elements in tissue remodeling in asthma and other inflammatory conditions in the airways.
Abstract: Background: Matrix metalloproteinases (MMPs) digest extracellular matrix components and might be important mediators of tissue remodeling. Proteinase activated receptor-2 (PAR-2) is expressed in a variety of cell types including epithelial cells. PAR-2 receptors are activated by serine proteases such as trypsin and mast cell tryptase and have been implicated in inflammation. Objective: To study the effects of PAR-2–mediated airway epithelial cell activation on the production of MMP-9. Methods: A specific PAR-2–activating peptide and trypsin were used to activate the human airway epithelial cell line A549 as well as primary cultures of small airway epithelial cells (SAEC). MMP-2 and MMP-9 messenger RNA and enzymatic activity were evaluated by RT-PCR and gelatin zymography, respectively. Results: PAR-2–activating peptides upregulated MMP-9 mRNA expression and release of MMP-9 enzymatic activity from airway epithelial cells but had no effect on MMP-2 production. Dexamethasone and budesonide (10 –6 to 10 –10 mmol) inhibited PAR-2–mediated MMP-9 release. Pretreatment with indomethacin indicated that MMP-9 release was not prostaglandin dependent. Inhibitors of the MAP kinase MEK- 1, and NFκB showed that both pathways are important for PAR-2–mediated MMP-9 release. Trypsin, a physiologic PAR-2 activator, upregulated MMP-9 but also MMP-2 release from airway epithelial cells. Conclusion: PAR-2 receptors appear to play an important role in the regulation of MMP-9 release from airway epithelial cells. As such, these receptors may be critical elements in tissue remodeling in asthma and other inflammatory conditions in the airways. (J Allergy Clin Immunol 2000;106:537-45.)

163 citations

Book
01 Sep 1986
TL;DR: A recent meeting focused on the ontogeny and differentiation of mast cells, their functional characteristics and the clinical and biological significance of their heterogeneity.
Abstract: Major differences between mast cells from different tissues and species have been known for at least 20 years but have been rigorously studied only recently. A recent meeting focused on the ontogeny and differentiation of mast cells, their functional characteristics and the clinical and biological significance of their heterogeneity.

151 citations

Journal ArticleDOI
01 Oct 2015-Thorax
TL;DR: This rich data set, linking prenatal and postnatal environments, diverse biological samples and rigorous phenotyping, will inform early developmental pathways to allergy, asthma and other chronic inflammatory diseases.
Abstract: The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study recruited 3624 pregnant women, most partners and 3542 eligible offspring. We hypothesise that early life physical and psychosocial environments, immunological, physiological, nutritional, hormonal and metabolic influences interact with genetics influencing allergic diseases, including asthma. Environmental and biological sampling, innate and adaptive immune responses, gene expression, DNA methylation, gut microbiome and nutrition studies complement repeated environmental and clinical assessments to age 5. This rich data set, linking prenatal and postnatal environments, diverse biological samples and rigorous phenotyping, will inform early developmental pathways to allergy, asthma and other chronic inflammatory diseases.

149 citations


Cited by
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01 Jan 2016
TL;DR: Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells as discussed by the authors, and the potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.
Abstract: Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

1,837 citations

Journal ArticleDOI
TL;DR: The role of flavonoids may transcend their presence in food as mentioned in this paper, however, the amount of quercetin that remains biologically available may not be of sufficient concentration, theoretically, to explain the beneficial effects seen with the Mediterranean diet.

1,546 citations

Journal ArticleDOI
23 Dec 2010-Cell
TL;DR: The data suggest that the "typical" phosphoprotein is widely expressed yet displays variable, often tissue-specific phosphorylation that tunes protein activity to the specific needs of each tissue, and is offered as an online resource for the biological research community.

1,520 citations

Journal ArticleDOI
TL;DR: Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort, and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

1,310 citations

Journal ArticleDOI
TL;DR: It is reported in a longitudinal human study that infants at risk of asthma have transient gut microbial dysbiosis during the first 100 days of life, and certain bacterial genera were decreased in these children, suggesting a potential causative role of the loss of these microbes.
Abstract: Asthma is the most prevalent pediatric chronic disease and affects more than 300 million people worldwide. Recent evidence in mice has identified a "critical window" early in life where gut microbial changes (dysbiosis) are most influential in experimental asthma. However, current research has yet to establish whether these changes precede or are involved in human asthma. We compared the gut microbiota of 319 subjects enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, and show that infants at risk of asthma exhibited transient gut microbial dysbiosis during the first 100 days of life. The relative abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia was significantly decreased in children at risk of asthma. This reduction in bacterial taxa was accompanied by reduced levels of fecal acetate and dysregulation of enterohepatic metabolites. Inoculation of germ-free mice with these four bacterial taxa ameliorated airway inflammation in their adult progeny, demonstrating a causal role of these bacterial taxa in averting asthma development. These results enhance the potential for future microbe-based diagnostics and therapies, potentially in the form of probiotics, to prevent the development of asthma and other related allergic diseases in children.

1,195 citations