Regional manifestations and control of the immune system

Saadi, Soheyla; Wrenshall, Lucile E.; Platt, Jeffrey L.

doi:10.1096/fj.01-0690hyp

Cited by 110 publications

(104 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These changes include diminished availability of oxygen (hypoxia) [8][9][10] with subsequent lactate accumulation and resultant metabolic acidosis. Such shifts in tissue metabolism result, at least in part, from profound recruitment of inflammatory cells, in particular myeloid cells such as neutrophils (polymorphonuclear cells) and monocytes.…”

Section: Hypoxia and Mucosal Inflammationmentioning

confidence: 99%

Hypoxia and gastrointestinal disease

2007

View full text Add to dashboard Cite

The gastrointestinal mucosa is a richly perfused vascular bed directly juxtaposed with the anaerobic and nonsterile lumen of the gut. As such, intestinal epithelial cells, which line the mucosa, experience a uniquely steep physiologic oxygen gradient in comparison with other cells of the body. Inflammation associated with a loss of epithelial barrier function and unregulated exposure of the mucosal immune system to luminal antigens leads to inflammatory bowel disease (IBD), a relatively common disorder with severe morbidity and a limited therapeutic repertoire. During IBD, increased tissue metabolism and vasculitis renders the chronically inflamed mucosa and particularly the epithelium hypoxic, giving rise to the activation of the hypoxia-responsive transcription factor hypoxia-inducible factor (HIF). Recent studies utilizing conditional intestinal epithelial hif1a-null mice have revealed a protective role for epithelial HIF-1α in murine models of IBD. Such protection occurs, at least in part, through HIF-dependent induction of barrier-protective genes in the epithelium. More recently, studies employing pharmacologic activation of HIF via inhibition of HIF prolyl hydroxylases revealed a profoundly protective effect of these agents in murine models of colitis. In this paper, we review this pathway in detail and examine the therapeutic potential for targeting HIF hydroxylases in intestinal mucosal inflammatory disease.

show abstract

Section: Hypoxia and Mucosal Inflammationmentioning

confidence: 99%

Hypoxia and gastrointestinal disease

2007

View full text Add to dashboard Cite

show abstract

“…22 HS displays a multifactoral affect on the immune response. 23 In the early events, HS is involved in the complement cascade and the containment and walling off of infection through interaction with complement and platelets. In the intermediate stage, the role of HS in inflammation involves the regulation of the formation of chemotactic complement proteins triggering neutrophils to respond to chemokines and release proteases and oxidants and endothelial expression of P-selectin promoting neutrophil adhesion.…”

Section: Glycosaminoglycans In Cellular Communication Linhardt and Toidamentioning

confidence: 99%

Role of Glycosaminoglycans in Cellular Communication

2004

View full text Add to dashboard Cite

Glycosaminoglycans are of critical importance in intercellular communication in organisms. This ubiquitous class of linear polyanions interacts with a wide variety of proteins, including growth factors and chemokines, which regulate important physiological processes. The presence of glycosaminoglycans on cell membranes and in the extracellular matrix also has resulted in their exploitation by infectious pathogens to gain access and entry into animal cells. This Account examines the structural and physical characteristics of these molecules responsible for their interaction with proteins important in cell-cell communication.

show abstract

“…Many studies have shown that inflammatory lesions are characterized by hypoxia (10)(11)(12)(13). Experimental studies further indicated that hypoxia directly activates the transcription of NF-κB and the expression of iNOS (14).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia regulates iNOS expression in human normal peritoneal and adhesion fibroblasts through nuclear factor kappa B activation mechanism

Jiang

Fletcher

Diamond

et al. 2009

Fertility and Sterility

View full text Add to dashboard Cite

Objective-To determine the mechanism by which hypoxia increases expression of iNOS in human normal peritoneal and adhesion fibroblasts.Design-Prospective experimental study. Setting-University medical center.Patient(s)-Primary cultures of fibroblasts from normal peritoneum and adhesion tissues. Intervention(s)-Hypoxia treated cells.Main Outcome Measure(s)-We utilized real-time RT-PCR to quantify mRNA levels of iNOS and NF-κB. Western blots were used to determine iNOS, NF-κB, IκB-α and phospho-IκB expression levels in normal peritoneal and adhesion fibroblasts in response to hypoxia.Result(s)-Hypoxia resulted in a significant increase in iNOS and NF-κB expression in normal and adhesion fibroblasts. Furthermore, both cell types manifested lower levels of NF-κB, cytoplasmic phospho-IκB-α, and iNOS proteins. In contrast, they manifested higher levels of cytoplasmic IκB-α and IκB-α/NF-κB ratios as well as phosphorylated-IκB-α/NF-κB ratio. Under hypoxic conditions, both cell types exhibited significantly decreased cytoplasmic NF-κB, IκB-α levels, and significantly increased cytoplasmic phospho-IκB-α, iNOS, and NF-κB protein levels.Conclusions-Hypoxia increases iNOS expression by a mechanism involving activation of NF-κB. The ratio of IκB-α/NF-κB or IκB-α/p-IκB-α can be used to monitor activation.

show abstract

Regional manifestations and control of the immune system

Cited by 110 publications

References 76 publications

Hypoxia and gastrointestinal disease

Hypoxia and gastrointestinal disease

Role of Glycosaminoglycans in Cellular Communication

Hypoxia regulates iNOS expression in human normal peritoneal and adhesion fibroblasts through nuclear factor kappa B activation mechanism

Contact Info

Product

Resources

About