A Central Role for Heme Oxygenase-1 in the Control of Intestinal Epithelial Chemokine Expression

Onyiah, Joseph C.; Schaefer, Rachel E M; Colgan, Sean P.

doi:10.1159/000488914

Cited by 12 publications

(12 citation statements)

References 47 publications

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“…Similarly, induction of HO-1 in IL10-/- mice reduced development of colitis [ 29 ]. Onyiah et al concentrated on the influence of modulating HO-1 expression on the inflammatory response of human intestinal epithelial cells (IECs) [ 30 ]. They observed that the deficiency of HO-1 in IECs resulted in increased proinflammatory chemokine expression, while the treatment of cells with an inducer of HO-1 inhibited this process, which suggests that HO-1 is a central regulator of IEC chemokine expression [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Onyiah et al concentrated on the influence of modulating HO-1 expression on the inflammatory response of human intestinal epithelial cells (IECs) [ 30 ]. They observed that the deficiency of HO-1 in IECs resulted in increased proinflammatory chemokine expression, while the treatment of cells with an inducer of HO-1 inhibited this process, which suggests that HO-1 is a central regulator of IEC chemokine expression [ 30 ]. In our study we observed a significant decrease in HO-1 level in the tissues of DSS-treated mice compared with control animals.…”

Section: Discussionmentioning

confidence: 99%

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New Class of Anti-Inflammatory Therapeutics Based on Gold (III) Complexes in Intestinal Inflammation–Proof of Concept Based on In Vitro and In Vivo Studies

Krajewska

Włodarczyk

Jacenik

et al. 2021

IJMS

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Inflammatory bowel diseases (IBD) are at the top of the worldwide rankings for gastrointestinal diseases as regards occurrence, yet efficient and side-effect-free treatments are currently unavailable. In the current study, we proposed a new concept for anti-inflammatory treatment based on gold (III) complexes. A new gold (III) complex TGS 121 was designed and screened in the in vitro studies using a mouse macrophage cell line, RAW264.7, and in vivo, in the dextran sulphate sodium (DSS)-induced mouse model of colitis. Physicochemical studies showed that TGS 121 was highly water-soluble; it was stable in water, blood, and lymph, and impervious to sunlight. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, the complex showed a potent anti-inflammatory profile, as evidenced in neutral red uptake and Griess tests. In the DSS-induced mouse model of colitis, the complex administered in two doses (1.68 μg/kg, intragastrically, and 16.8 μg/kg, intragastrically, once daily) produced a significant (* p < 0.05) anti-inflammatory effect, as shown by macroscopic score. The mechanism of action of TGS 121 was related to the enzymatic and non-enzymatic antioxidant system; moreover, TGS 121 induced changes in the tight junction complexes expression in the intestinal wall. This is the first study proving that gold (III) complexes may have therapeutic potential in the treatment of IBD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

New Class of Anti-Inflammatory Therapeutics Based on Gold (III) Complexes in Intestinal Inflammation–Proof of Concept Based on In Vitro and In Vivo Studies

Krajewska

Włodarczyk

Jacenik

et al. 2021

IJMS

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“…In addition, heme is a nutritionally derived macromolecule present in the intestinal lumen in meat eating species. It is metabolized by heme oxygenase-1, that plays a central role in the regulation of epithelial inflammation [28] and is inducible by inflammatory context [29]. The tissue concentration can therefore decrease in the event of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Multimodal imaging as optical biopsy system for gastritis diagnosis in humans, and input of the mouse model

et al. 2021

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Background: Gastric inflammation is a major risk factor for gastric cancer. Current endoscopic methods are not able to efficiently detect and characterize gastric inflammation, leading to a sub-optimal patients' care. New non-invasive methods are needed. Reflectance mucosal light analysis is of particular interest in this context. The aim of our study was to analyze reflectance light and specific autofluorescence signals, both in humans and in a mouse model of gastritis. Methods: We recruited patients undergoing gastroendoscopic procedure during which reflectance was analysed with a multispectral camera. In parallel, the gastritis mouse model of Helicobacter pylori infection was used to investigate reflectance from ex vivo gastric samples using a spectrometer. In both cases, autofluorescence signals were measured using a confocal microscope. Findings: In gastritis patients, reflectance modifications were significant in near-infrared spectrum, with a decrease between 610 and 725 nm and an increase between 750 and 840 nm. Autofluorescence was also modified, showing variations around 550 nm of emission. In H. pylori infected mice developing gastric inflammatory lesions, we observed significant reflectance modifications 18 months after infection, with increased intensity between 617 and 672 nm. Autofluorescence was significantly modified after 1, 3 and 6 months around 550 and 630 nm. Both in human and in mouse, these reflectance data can be considered as biomarkers and accurately predicted inflammatory state. Interpretation: In this pilot study, using a practical measuring device, we identified in humans, modification of reflectance spectra in the visible spectrum and for the first time in near-infrared, associated with inflammatory gastric states. Furthermore, both in the mouse model and humans, we also observed modifications of autofluorescence associated with gastric inflammation. These innovative data pave the way to deeper validation studies on larger cohorts, for further development of an optical biopsy system to detect gastritis and finally to better surveil this important gastric cancer risk factor. Funding: The project was funded by the ANR EMMIE (ANR-15-CE17-0015) and the French Gastroenterology Society (SNFGE).

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“…Carbon monoxide (CO) is currently known to be generated in cells or tissues as a byproduct of heme oxygenase (HO) after heme catalytic activity [6] . Even though CO is toxic to humans at high concentrations, many studies have documented that low-doses exogenous CO (approximately 250–500 ppm) have protective function against various human diseases [7] , [8] .…”

Section: Introductionmentioning

confidence: 99%

Carbon monoxide releasing molecule-2 attenuates Pseudomonas aeruginosa-induced ROS-dependent ICAM-1 expression in human pulmonary alveolar epithelial cells

Lee¹,

Chiang³

et al. 2018

Redox Biology

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Pseudomonas aeruginosa (P. aeruginosa) infection in the lung is common in patients with cystic fibrosis (CF). Intercellular adhesion molecule-1 (ICAM-1) is known to play a key role in lung inflammation. Acute inflammation and its timely resolution are important to ensure bacterial clearance and limit tissue damage. Carbon monoxide (CO) has been shown to exert anti-inflammatory effects in various tissues and organ systems. Here, we explored the protective effects and mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on P. aeruginosa-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs). We showed that P. aeruginosa induced prostaglandin E2 (PGE2)/interleukin-6 (IL-6)/ICAM-1 expression and monocyte adherence to HPAEpiCs. Moreover, P. aeruginosa-induced inflammatory responses were inhibited by transfection with siRNA of Toll-like receptor 4 (TLR4), PKCα, p47phox, JNK2, p42, p50, or p65. P. aeruginosa also induced PKCα, JNK, ERK1/2, and NF-κB activation. We further demonstrated that P. aeruginosa increased intracellular ROS generation via NADPH oxidase activation. On the other hand, P. aeruginosa-induced inflammation was inhibited by pretreatment with CORM-2. Preincubation with CORM-2 had no effects on TLR4 mRNA levels in response to P. aeruginosa. However, CORM-2 inhibits P. aeruginosa-induced inflammation by decreasing intracellular ROS generation. P. aeruginosa-induced PKCα, JNK, ERK1/2, and NF-κB activation was inhibited by CORM-2. Finally, we showed that P. aeruginosa induced levels of the biomarkers of inflammation in respiratory diseases, which were inhibited by pretreatment with CORM-2. Taken together, these data suggest that CORM-2 inhibits P. aeruginosa-induced PGE2/IL-6/ICAM-1 expression and lung inflammatory responses by reducing the ROS generation and the inflammatory pathways.

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A Central Role for Heme Oxygenase-1 in the Control of Intestinal Epithelial Chemokine Expression

Cited by 12 publications

References 47 publications

New Class of Anti-Inflammatory Therapeutics Based on Gold (III) Complexes in Intestinal Inflammation–Proof of Concept Based on In Vitro and In Vivo Studies

New Class of Anti-Inflammatory Therapeutics Based on Gold (III) Complexes in Intestinal Inflammation–Proof of Concept Based on In Vitro and In Vivo Studies

Multimodal imaging as optical biopsy system for gastritis diagnosis in humans, and input of the mouse model

Carbon monoxide releasing molecule-2 attenuates Pseudomonas aeruginosa-induced ROS-dependent ICAM-1 expression in human pulmonary alveolar epithelial cells

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