Cytokines Modulate the “Immune-Metabolism” Interactions during Behçet Disease: Effect on Arginine Metabolism

Belguendouz, Houda; Lahmar-Belguendouz, K.; Messaoudene, D.; Djeraba, Zineb; Otmani, F.; Hakem, D.; Lahlou-Boukoffa, O.S.; Youinou, Pierre; Touil-Boukoffa, Chafia

doi:10.1155/2015/241738

Cited by 16 publications

(6 citation statements)

References 46 publications

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“…We measured the PBMC expression levels of IL-6, IL-8, IL-10, IL-1β, TNF-α and MCP-1 by ELISA. These cytokines have all been shown to play a role in the development of BD as shown by earlier studies 22 23 . Carriers of the CC genotype had a higher secretion level of IL-10 as compared to GG and CG carriers (P = 0.017, Fig.…”

Section: Resultsmentioning

confidence: 62%

Genetic Variations of NLR family genes in Behcet’s Disease

Jiang

et al. 2016

Sci Rep

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This study aimed to investigate whether single nucleotide polymorphisms (SNPs) of five NLR family genes (NOD1, NOD2, NLRP1, NLRP3 and CIITA) are associated with Behcet’s disease (BD) in a Chinese Han population. The study was carried out in 950 BD patients and 1440 controls for 19 SNPs in the selected NLR genes. In the first-stage study, significantly decreased frequencies of the CIITA//rs12932187 C allele (Pc = 1.668E-02) and NOD1//rs2075818 G allele (Pc = 4.694E-02) were found in BD patients as compared to controls . After performing a second stage validation study and combination of data we confirmed the association of CIITA//rs12932187 and NOD1//rs2075818 with BD. In CIITA//rs12932187, the frequencies of the CC genotype and C allele were significantly lower in BD than in controls (Pc = 3.331E-06; Pc = 6.004E-07, respectively). In NOD1//rs2075818, the GG genotype and G allele showed significantly decreased frequencies in BD patients when compared to controls (Pc = 1.022E-02; Pc = 6.811E-05, respectively). Functional experiments showed that carriers with the CC genotype in CIITA//rs12932187 had a lower CIITA mRNA expression level and an enhanced IL-10 secretion as compared to GG and CG carriers. This study provides evidence that the CIITA and NOD1 gene are involved in the susceptibility to Behcet’s disease.

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Section: Resultsmentioning

confidence: 62%

Genetic Variations of NLR family genes in Behcet’s Disease

Jiang

et al. 2016

Sci Rep

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“…As a result of protein catabolism there will be an increase in tissue nitrogen load. Despite the requirement for nitrogen for acute phase proteins, there appears to be a tendency to increase nitrogen excretion through upregulation of the urea cycle in proinflammatory states (57)(58)(59). Our findings suggest urea increases and aspartate decreases as CRP increases, which supports the finding of increased urea cycle activity during systemic inflammation.…”

Section: Discussionsupporting

confidence: 77%

Relationship Between Inflammation and Metabolism in Patients With Newly Presenting Rheumatoid Arthritis

et al. 2021

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BackgroundSystemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy–based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA.MethodsSerum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation.ResultsUsing PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP.ConclusionsThis study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets.

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“…Immune-metabolic interactions are critical regulators of pathophysiological conditions, including skin inflammatory disorders (Alwarawrah et al, 2018, Belguendouz et al, 2015, Ganeshan and Chawla, 2014. Metabolic processes underlie distinct immune cell functions J o u r n a l P r e -p r o o f (Matarese et al, 2014).…”

Section: Introductionmentioning

confidence: 99%