Increased Expression of the Chemokine Fractalkine in Crohn's Disease and Association of the Fractalkine Receptor T280M Polymorphism with a Fibrostenosing Disease Phenotype

Brand, Stephan; Hofbauer, Katrin; Dambacher, Julia; Schnitzler, Fabian; Staudinger, Tanja; Pfennig, Simone; Seiderer, Julia; Tillack, Cornelia; Konrad, Astrid; Göke, Burkhard; Ochsenkühn, Thomas; Lohse, Peter

doi:10.1111/j.1572-0241.2005.00361.x

Cited by 94 publications

(83 citation statements)

References 33 publications

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“…28 In addition, we demonstrated that the T280M polymorphism in the CX3CR1 gene, which encodes the receptor for the chemokine fractalkine, is also associated with ileal disease. 18 This is consistent with the essential role of CX3CR1-expressing dendritic cells in the luminal sampling of bacteria in the terminal ileum which we demonstrated in a previous study. 42 These observations suggest that genetic variants, which are associated with deficits in the recognition of the intestinal bacteria or bacterial products, are associated with a predominant ileal disease location, triggered by the 10 3 -to 10 4 -fold increase of microbial density from the terminal ileum to the colon.…”

Section: Discussionsupporting

confidence: 74%

“…45 However, functional studies are needed to analyse if the +1059 G/C polymorphism leads to an impaired recognition of bacteria by CRP which would explain a similar CD phenotype as observed for the 1007fs CARD15 variant 28 and the T280M CX3CR1 genotype. 18 The influence of the CRP +1059G/C polymorphism on CD has not been studied so far. Here, we demonstrate that the presence of a C allele, particularly in male patients and CD patients with a CDAI < 150, is associated with lower serum CRP levels.…”

Section: Discussionmentioning

confidence: 99%

“…13 Recently, we demonstrated that polymorphisms in certain genes involved in the acute phase response during inflammation are associated with particular CD subtypes. [17][18][19] Therefore, we analysed if polymorphisms in the gene encoding CRP, the prototypic acute phase response protein, are also associated with CD and certain CD phenotypes. We focused on the CRP (G fi C) +1059 SNP in exon 2, which is so far the most extensively characterized CRP SNP and has been shown to decrease CRP serum levels 15 while in contrast no association for three other CRP polymorphisms ()717G/A, 1444C/T, CRP 4A/G) with CD and CRP levels after infliximab treatment could be demonstrated in CD patients.…”

Section: Introductionmentioning

confidence: 99%

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The +1059G/C polymorphism in the C‐reactive protein (CRP) gene is associated with involvement of the terminal ileum and decreased serum CRP levels in patients with Crohn's disease

Thalmaier

Dambacher

Seiderer

et al. 2006

Aliment Pharmacol Ther

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The +1059G/C polymorphism in the C‐reactive protein (CRP) gene is associated with involvement of the terminal ileum and decreased serum CRP levels in patients with Crohn's disease

Thalmaier

Dambacher

Seiderer

et al. 2006

Aliment Pharmacol Ther

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“…This pattern of expression mirrors that found in epithelial cells of biliary ductules (44) but differs markedly from that of intestinal epithelial cells, where CX 3 CL1 largely is expressed in the basolateral membrane and in regions of intercellular contact (45,46). In the intestine, as in the kidney, expression of CX 3 CL1 is highly enhanced in disease states that are marked by active inflammation (14,45,47).…”

Section: Discussionmentioning

confidence: 62%

Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

Durkan¹,

Alexander²,

Liu³

et al. 2007

Journal of the American Society of Nephrology

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The chemokine CX 3 CL1 plays a key role in glomerulonephritis and can act as both chemoattractant and adhesion molecule. CX 3 CL1 also is upregulated in tubulointerstitial injury, but little is known about the subcellular distribution and function of CX 3 CL1 in renal tubular epithelial cells (RTEC). Unexpectedly, it was found that CX 3 CL1 is expressed predominantly on the apical surface of tubular epithelium in human renal transplant biopsy specimens with acute rejection or acute tubular necrosis. For studying the targeting of CX 3 CL1 in polarized RTEC, MDCK cells that expressed untagged or green fluorescent protein-tagged CX 3 CL1 were generated. The chemokine was present on the apical membrane and in subapical vesicles. Apical targeting of CX 3 CL1 was not due to signals that were conferred by its intracellular domain, to associations with lipid rafts, or to O-glycosylation but, rather, depended on N-linked glycosylation of the protein. With the use of fluorescence recovery after photobleaching, it was found that CX 3 CL1 is immobile in the apical membrane. However, CX 3 CL1 partitioned with the triton-soluble rather than -insoluble cellular fraction, indicating that it is not associated directly with the actin cytoskeleton or with lipid rafts. Accordingly, disruption of rafts through cholesterol depletion did not render CX 3 CL1 mobile. For exploration of potential functions of apical CX 3 CL1, binding of CX 3 CR1-expressing leukocytes to polarized RTEC was examined. Leukocyte adhesion to the luminal surface was enhanced significantly when CX 3 CL1 was present. These data demonstrate that CX 3 CL1 is expressed preferentially on the apical membrane of RTEC and suggest a novel function for the chemokine in recruitment and retention of leukocytes in tubulointerstitial inflammation.

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“…For example, CX3CR1 polymorphisms have been implicated in conditions such as Crohn's disease, multiple sclerosis, and bronchiolitis among Caucasians [25][26][27]. Further downplaying the possible role of CX3CR1 genetic polymorphism on HIV infection, no significant differences in CX3CR1 745G>A genotype and allele frequencies between HIV EI and EU children were observed (Table 3).…”

Section: Chemokine Receptor Polymorphism and Their Association With Hmentioning

confidence: 83%

CCR2, CX3CR1, RANTES and SDF1 genetic polymorphisms influence HIV infection in a Zimbabwean pediatric population

Mhandire

Duri

Kandawasvika

et al. 2014

J Infect Dev Ctries

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Introduction: There is growing evidence that polymorphisms in chemokine and chemokine receptor genes influence susceptibility to HIV infection and disease progression. However, not much is documented about the prevalence and effects of chemokine and chemokine receptor gene variations in the Zimbabwean population despite the high burden of HIV/AIDS in the country. This study therefore describes polymorphisms in CCR2, CX3CR1, SDF1 and RANTES genes in a Zimbabwean pediatric population and their effects on HIV infection in children born to HIV-infected mothers. Methodology: A total of 106 children between seven and nine years of age comprising 70 perinatally exposed to HIV (34 born infected [EI] and 36 born uninfected [EU]) and 36 unexposed and uninfected (UEUI) controls were recruited. Six allelic variants in four genes were genotyped using PCR-RFLP and sequencing. Results: Frequencies for minor alleles in the HIV uninfected groups (EU and UEUI) were CCR2 190A (16%), SDF1 801A (2%), CX3CR1 745A (9%), CX3CR1 839T (0%), RANTES In 1.1C (20%), and RANTES -403A (44%). There were significant differences between the EI and EU groups in the distribution of CCR2 190G/A genotype (15% versus 39%, respectively, p = 0.02) and CCR2 190G/A-CX3CR1 745G/G genotype combination (0% versus 33%, respectively, p = 0.002). Conclusions: Our findings suggest that chemokine and chemokine receptor gene variants seem to play an important role in the dynamics of HIV infection and could be used as drug or vaccine targets.

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Increased Expression of the Chemokine Fractalkine in Crohn's Disease and Association of the Fractalkine Receptor T280M Polymorphism with a Fibrostenosing Disease Phenotype

Abstract: The expression of the chemokine fractalkine is upregulated by proinflammatory cytokines and enhanced in inflamed CD lesions. The CX3CR1 T280M polymorphism appears to influence CD phenotype and localization.

Cited by 94 publications

References 33 publications

The +1059G/C polymorphism in the C‐reactive protein (CRP) gene is associated with involvement of the terminal ileum and decreased serum CRP levels in patients with Crohn's disease

The +1059G/C polymorphism in the C‐reactive protein (CRP) gene is associated with involvement of the terminal ileum and decreased serum CRP levels in patients with Crohn's disease

Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

CCR2, CX3CR1, RANTES and SDF1 genetic polymorphisms influence HIV infection in a Zimbabwean pediatric population

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