Dataset Information

Point-of-Care Monitoring of Colitis Using Intestinal Alkaline Phosphatase in Inflammatory Bowel Disease.

ABSTRACT: Intestinal Alkaline Phosphatase (IAP) was investigated as a potential biomarker to monitor colitis in a mouse model of Inflammatory Bowel Disease (IBD). We developed a Point-Of-Care (POC) assay to detect IAP with a glucose meter in 15 min. We synthesized a paracetamol-bearing compound specifically cleaved by IAP to release paracetamol, which can be detected with a personal glucometer. Interleukin 10 deficient (IL 10-/-) mouse model samples were used to compare the IAP level in mice with mild or severe colitis. The results showed that fecal IAP level was significantly lower in each mouse sample with severe colitis than with mild colitis. Mice treated with anti-Tumor Necrosis Factor-alpha (anti-TNF-α) to decrease inflammation exhibited a much higher level of IAP than those without treatment (IAP levels from anti-TNF-α treated vs nontreated = 2.80 U vs 0.11 U, P < 0.0001). Taken together, IAP can be considered as a potential biomarker to monitor colitis, and a rapid, user-friendly POC glucometer-based assay can be potentially used to monitor colitis levels and inflammation flareups in IBD.

SUBMITTER: Sheng X

PROVIDER: S-EPMC8628551 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Point-of-Care Monitoring of Colitis Using Intestinal Alkaline Phosphatase in Inflammatory Bowel Disease.

Sheng Xiaolin X Liu Dandan D Gamage Sujani K SK Luo Ying Y Viennois Emilie E Merlin Didier D Iyer Suri S SS

ACS sensors 20210226 3

Intestinal Alkaline Phosphatase (IAP) was investigated as a potential biomarker to monitor colitis in a mouse model of Inflammatory Bowel Disease (IBD). We developed a Point-Of-Care (POC) assay to detect IAP with a glucose meter in 15 min. We synthesized a paracetamol-bearing compound specifically cleaved by IAP to release paracetamol, which can be detected with a personal glucometer. Interleukin 10 deficient (IL 10-/-) mouse model samples were used to compare the IAP level in mice with mild or ...[more]

PMID: 33635063

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Project description:Tissue-nonspecific alkaline phosphatase (TNAP) is necessary for skeletal mineralization by its ability to hydrolyze the mineralization inhibitor inorganic pyrophosphate (PPi), which is mainly generated from extracellular ATP by ectonucleotide pyrophosphatase phosphodiesterase 1 (NPP1). Since children with TNAP deficiency develop bone metaphyseal auto-inflammations in addition to rickets, we hypothesized that TNAP also exerts anti-inflammatory effects relying on the hydrolysis of pro-inflammatory adenosine nucleotides into the anti-inflammatory adenosine. We explored this hypothesis in bone metaphyses of 7-day-old Alpl+/- mice (encoding TNAP), in mineralizing hypertrophic chondrocytes and osteoblasts, and non-mineralizing mesenchymal stem cells (MSCs) and neutrophils, which express TNAP and are present, or can be recruited in the metaphysis. Bone metaphyses of 7-day-old Alpl+/- mice had significantly increased levels of Il-1? and Il-6 and decreased levels of the anti-inflammatory Il-10 cytokine as compared with Alpl+/+ mice. In bone metaphyses, murine hypertrophic chondrocytes and osteoblasts, Alpl mRNA levels were much higher than those of the adenosine nucleotidases Npp1, Cd39 and Cd73. In hypertrophic chondrocytes, inhibition of TNAP with 25 ?M of MLS-0038949 decreased the hydrolysis of AMP and ATP. However, TNAP inhibition did not significantly modulate ATP- and adenosine-associated effects in these cells. We observed that part of TNAP proteins in hypertrophic chondrocytes was sent from the cell membrane to matrix vesicles, which may explain why TNAP participated in the hydrolysis of ATP but did not significantly modulate its autocrine pro-inflammatory effects. In MSCs, TNAP did not participate in ATP hydrolysis nor in secretion of inflammatory mediators. In contrast, in neutrophils, TNAP inhibition with MLS-0038949 significantly exacerbated ATP-associated activation and secretion of IL-1?, and extended cell survival. Collectively, these results demonstrate that TNAP is a nucleotidase in both hypertrophic chondrocytes and neutrophils, and that this nucleotidase function is associated with autocrine effects on inflammation only in neutrophils.

Dataset Information

Point-of-Care Monitoring of Colitis Using Intestinal Alkaline Phosphatase in Inflammatory Bowel Disease.

Publications

Point-of-Care Monitoring of Colitis Using Intestinal Alkaline Phosphatase in Inflammatory Bowel Disease.

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