Chris Juul Hedegaard

Publications (3)11.1 Total impact

• Source

  Available from: Claus Henrik Nielsen

  Article: Variation in NOD2 augments Th2- and Th17 responses to myelin basic protein in multiple sclerosis.

  Chris Juul Hedegaard, Christian Enevold, Finn Sellebjerg, Klaus Bendtzen, Claus Henrik Nielsen
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  ABSTRACT: Variations in the gene for the nucleotide-binding oligomerisation domain (NOD) 2 have been associated with Crohn's disease but not multiple sclerosis (MS). Here we investigate the effect of three polymorphisms in the NOD2 gene (rs5743277, rs2066842 and rs5743291) on cytokine production and CD4+ T cell proliferation elicited by human myelin basic protein (MBP) in blood mononuclear cell (MNC) cultures from 29 patients with MS. No polymorphism was observed at rs5743277. No associations with the rs2066842 polymorphism were found. Concerning rs5743291, none were homozygous for the minor allele. Seven of 29 (24%) patients were heterozygous, and five of these (71%) exhibited increased MBP-induced CD4+ T cell proliferation versus four of 22 (18%), who were homozygous for the major allele (p<0.04). Interleukin (IL)-5 was induced by MBP in MNC from the same five carriers versus two (9%) homozygotes (p<0.004); four carriers (57%) versus three non-carriers (14%) exhibited IL-17 responses to MBP (p<0.04). By contrast, we found no association between the polymorphisms investigated and interferon-gamma-, tumor necrosis factor-alpha-, IL-2, -4- or IL-10 responses to MBP. These results indicate that the rs5743291 polymorphism influences T helper (Th) cell 2- and Th17 cell responses in MNC from MS patients.
  PLoS ONE 01/2011; 6(5):e20253. · 4.09 Impact Factor
• Article: Serum levels of C-reactive protein in adolescents with periodontitis.

  Rodrigo López, Vibeke Baelum, Chris Juul Hedegaard, Klaus Bendtzen
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  ABSTRACT: The results of several cross-sectional studies suggested a relationship between periodontitis and higher serum levels of C-reactive protein (CRP). Most of these studies were restricted to adult study groups with severe periodontal inflammation, and the potential effects of confounding factors were frequently overlooked. A case-referent study comprised of 87 adolescent cases who presented with clinical attachment loss ≥3 mm recorded in ≥2 of 16 teeth and 73 controls who did not fulfill these criteria was nested in a fully enumerated adolescent population. Venous blood samples were obtained, and CRP levels were quantified, using a high-sensitive bead-based flow cytometric assay. The Mann-Whitney U test was used to assess overall differences between groups. The median serum CRP values for cases and controls were 64 ng/ml (interquartile range: 27 to 234 ng/ml) and 55 ng/ml (31 to 183 ng/ml), respectively (P = 0.8). Serum levels of CRP were not significantly higher among subjects with periodontitis than among controls. However, a statistically significant positive association between percentages of sites with bleeding on probing and log-transformed CRP values was observed.
  Journal of Periodontology 11/2010; 82(4):543-9. · 2.60 Impact Factor
• Article: Effects of spironolactone on human blood mononuclear cells: mineralocorticoid receptor independent effects on gene expression and late apoptosis induction.

  Søren Ulrik Salling Sønder, Marianne Mikkelsen, Klaus Rieneck, Chris Juul Hedegaard, Klaus Bendtzen
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  ABSTRACT: 1 Spironolactone (SPIR) binds to cytoplasmic mineralocorticoid receptors (MR) and functions as an aldosterone antagonist. Recently, the drug was shown to have an early suppressive effect on several immunoactive and proinflammatory cytokines. 2 To elucidate the mechanism behind this, the four MR-binding steroids SPIR, canrenone, 7alpha-thiomethyl-spironolactone and aldosterone (ALDO) were investigated for effects on lipopolysaccharide- and phytohemagglutinin-A-activated human blood mononuclear cells. Gene expression was examined after 4 h using microarrays, and SPIR affected 1018 transcripts of the (=) 22,000 probed. In contrast, the SPIR-related steroids affected 17 or fewer transcripts. Combining SPIR and ALDO resulted in 940 affected transcripts, indicating that SPIR has an early gene-regulatory effect independent of MR. 3 The affected genes encode a large number of signalling proteins and receptors, including immunoinflammatory response genes and apoptosis and antiapoptosis genes. Apoptosis was evident in CD3-, CD14- and CD19-positive cells, but only after 18 h of exposure to SPIR. 4 The transcriptional network involving the differentially regulated genes was examined and the results indicate that SPIR affects genes controlled by the transcription factors NF-kappaB, CEBPbeta and MYC. 5 These observations provide new insight into the non-MR-mediated effects of SPIR.
  British Journal of Pharmacology 06/2006; 148(1):46-53. · 4.41 Impact Factor