Expression of platelet P-selectin and detection of soluble P-selectin, NPY and RANTES in patients with inflammatory bowel disease

Fägerstam, J Patrik; Whiss, Per A; Ström, Magnus; Andersson, Rgg

doi:10.1007/s000110050618

Cited by 46 publications

(31 citation statements)

References 37 publications

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“…Furthermore, platelets from inflammatory bowel disease (IBD) patients are more sensitive to platelet agonists in vitro (van Wersch et al, 1990), while the plateletspecific chemokines PF-4 and b-TG are detected in plasma, revealing activation in vivo (Collins et al, 1994;Vrij et al, 2000). A role for platelets in mediating leukocyte recruitment to the inflamed colon is likely since platelet P-selectin and RANTES are also detected (Fagerstam et al, 2000), and this is localized to the intestinal microcirculation (Collins et al, 1997). Recent evidence suggests that increased circulating levels of soluble CD40L are of platelet origin in IBD patients (Danese et al, 2003a).…”

Section: Platelet Activation In Inflammatory Bowel Diseasementioning

confidence: 99%

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Pitchford

2007

British J Pharmacology

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An alteration in the character and function of platelets is manifested in patients with inflammatory diseases, and these alterations have been dissociated from the well‐characterized involvement of platelets in thrombosis and haemostasis. Recent evidence reveals platelet activation is sometimes critical in the development of inflammation. The mechanisms by which platelets participate in inflammation are diverse, and offer numerous opportunities for future drug intervention. There is now acceptance that platelets act as innate inflammatory cells in immune responses, with roles as sentinel cells undergoing surveillance, responding to microbial invasion, orchestrating leukocyte recruitment, and migrating through tissue, causing damage and influencing repair processes in chronic disease. Some of these processes are targeted by drugs that are being developed to target platelet participation in atherosclerosis. The actions of platelets therefore influence the pathogenesis of diverse inflammatory diseases in various body compartments, encompassing parasitic and bacterial infection, allergic inflammation (especially asthma and rhinitis), and non‐atopic inflammatory conditions, for example, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and atherosclerosis. This review will first discuss the evidence for platelet activation in these various inflammatory diseases, and secondly discuss the mechanisms by which this pathogenesis occurs and the various anti‐platelet agents which have been developed to combat platelet activation in atherosclerosis and their potential future use for the treatment of other inflammatory diseases.British Journal of Pharmacology (2007) 152, 987–1002; doi:10.1038/sj.bjp.0707364; published online 2 July 2007

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Section: Platelet Activation In Inflammatory Bowel Diseasementioning

confidence: 99%

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Pitchford

2007

British J Pharmacology

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“…Although anti-TNF-␣ antibodies, such as infliximab, appear safe and efficacious, the same characteristics of other biological therapies remain to be evaluated. Since upregulation of both of P-and E-selectin has been reported in patients with active IBD (11,12,15), selectin blockade appears an attractive approach in IBD management. Although P-selectin blockade is effective in attenuating ischemia-reperfusion injury and indomethacin-induced gastropathy, anti-P-selectin antibody treatment did not provide significant protection in trinitrobenzene sulfonic acid-induced colitis, despite abrogating leukocyte adhesion (39).…”

Section: Discussionmentioning

confidence: 99%

Exploring the interplay of barrier function and leukocyte recruitment in intestinal inflammation by targeting fucosyltransferase VII and trefoil factor 3

Beck

Ihara

Hirota

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Intestinal mucosal integrity is dependent on epithelial function and a regulated immune response to injury. Fucosyltransferase VII (Fuc-TVII) is an essential enzyme required for the expression of the functional ligand for E- and P-selectin. Trefoil factor 3 (TFF3) is involved in both protecting the intestinal epithelium against injury as well as aiding in wound repair following injury. The aim of the present study was to assess the interplay between barrier function and leukocyte recruitment in intestinal inflammation. More specifically, we aimed to examine how targeted disruption of Fuc-TVII either in wild-type or TFF3−/− mice would alter their susceptibility to colonic injury. TFF3 and Fuc-TVII double-knockout mice (TFF3/Fuc-TVII−/− mice) were generated by mating TFF3−/− and Fuc-TVII−/− mice. Colitis was induced by administration of dextran sodium sulfate (DSS) (2.5% wt/vol) in the drinking water. Changes in baseline body weight, diarrhea, and fecal blood were assessed daily. Upon euthanasia, extents of colonic inflammation were assessed macroscopically, microscopically, and through quantification of myeloperoxidase (MPO) activity. Colonic lymphocyte subpopulations were assessed at 6 days after administration of DSS by flow cytometry and immunohistochemistry. No baseline intestinal inflammation was found in TFF3/Fuc-TVII−/−, TFF3−/−, Fuc-TVII−/−, or wild-type mice. Loss of Fuc-TVII resulted in a reduction in disease severity whereas TFF3−/− mice were markedly more susceptible to DSS-induced colitis. Remarkably, the loss of Fuc-TVII in TFF3−/− mice markedly decreased the severity of DSS-induced colitis as evidenced by reduced weight loss, diarrhea, decreased colonic MPO levels and improved survival. Furthermore, the loss of TFF3 resulted in increased severity of spontaneous colitis in IL-2/β-microglobulin-deficient mice. These studies highlight the importance of the interplay between factors involved in the innate immune response, mucosal barrier function, and genes involved in regulating leukocyte recruitment and other aspects of the immune response.

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“…Total colonic mucosa of patients with UC (13,14) and a lower plasma concentration of the RANTES chemokine following 5-ASA medication in patients with IBD suggests that this chemokine may play a significant role in the pathogenesis of IBD (15).…”

Section: Rantes Genotype N or (95% Ci) Or (95% Ci) -----------------mentioning

confidence: 99%

“…Previous studies have reported that the expression of RANTES is enhanced in the colonic mucosa of patients with UC (13,14). In addition, it was reported that treatment with 5-aminosalicylic acid (ASA) medication in IBD patients resulted in a lower plasma concentration of RANTES, indicating that this is a beneficial product of 5-ASA treatment (15 (19,20). However, there have been no studies regarding the association between the RANTES promoter polymorphism and UC.…”

Section: Introductionmentioning

confidence: 99%

Effect of RANTES gene promoter genotypes in patients with ulcerative colitis

et al. 2014

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Abstract.A complex interaction of genetic and environmental factors is closely associated with the development of inflammatory bowel disease. Previous studies reported that the expression of the regulated upon activation, normal T-cell expressed and secreted (RANTES) gene is enhanced in the colonic mucosa of ulcerative colitis (UC). Quantitative differences in RANTES gene expression among numerous promoter genotypes have also been reported. The aim of the present study was to clarify the effect of RANTES promoter polymorphism on the risk of UC, including its clinical phenotypes. A total of 150 UC patients and 372 healthy control (HC) subjects participated in the study. The UC patients were classified by disease behavior, severity and extent of disease. Restriction fragment length polymorphism analysis was performed for polymorphisms at -28 C/G in the RANTES gene promoter region. Although no significant difference of the RANTES promoter genotype distribution was observed between the HC and UC groups, the G/G genotype was significantly higher among female (OR=3.95, 95% CI=1.22-12.82, P=0.03), non-steroid dependent (OR=3.37, 95% CI=1.16-9.85, P= 0.03) and non-refractory (OR=3.76, 95% CI=1.29-10.98, P=0.02) UC patients. The G carrier was also found to be associated with an increased risk of rectal colitis (OR=2.21, 95% CI=1.12-4.39, P= 0.03). The data indicate that the polymorphism of the RANTES promoter is not directly associated with the susceptibility to UC, but the -28 G allele is associated with female UC patients and mild clinical phenotypes of UC, including non-steroid dependency, non-refractory and rectal colitis.

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Expression of platelet P-selectin and detection of soluble P-selectin, NPY and RANTES in patients with inflammatory bowel disease

Cited by 46 publications

References 37 publications

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Exploring the interplay of barrier function and leukocyte recruitment in intestinal inflammation by targeting fucosyltransferase VII and trefoil factor 3

Effect of RANTES gene promoter genotypes in patients with ulcerative colitis

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