Anti-inflammatory effect of Tauroursodeoxycholic acid in RAW 264.7 macrophages, Bone marrow-derived macrophages, BV2 microglial cells, and spinal cord injury

Kim, Seong Jun; Ko, Wan‐Kyu; Jo, Min-Jae; Arai, Yoshie; Choi, Hyemin; Kumar, Hemant; Han, Inbo; Sohn, Seil

doi:10.1038/s41598-018-21621-5

Cited by 38 publications

(51 citation statements)

References 32 publications

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“…We surmise that induction of ER stress in goblet cells is functionally relevant to the detrimental effects of MDX because pretreatment of mice with TUDCA, a chemical chaperone that inhibits ER stress, prevented MDX-mediated Ern-2 RNA overexpression and Muc-2 protein down-regulation, as well as the detrimental effect of MDX on DSS-induced colitis. Because TUDCA was reported to exert other protective functions in the gut (eg, reduction of proinflammatory cytokine synthesis and improvement of intestinal barrier function),39, 40 we cannot exclude the possibility that TUDCA-mediated prevention of intestinal damage in colitic mice receiving MDX can in part rely on other potential regulatory effects of the compound.…”

Section: Discussionmentioning

confidence: 99%

The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress–Driven Mucus Depletion and Exacerbates Intestinal Inflammation

Laudisi

Fusco

Dinallo

et al. 2019

Cellular and Molecular Gastroenterology and Hepatology

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Background & AimsFood additives, such as emulsifiers, stabilizers, or bulking agents, are present in the Western diet and their consumption is increasing. However, little is known about their potential effects on intestinal homeostasis. In this study we examined the effect of some of these food additives on gut inflammation.MethodsMice were given drinking water containing maltodextrin (MDX), propylene glycol, or animal gelatin, and then challenged with dextran sulfate sodium or indomethacin. In parallel, mice fed a MDX-enriched diet were given the endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA). Transcriptomic analysis, real-time polymerase chain reaction, mucin-2 expression, phosphorylated p38 mitogen-activated protein (MAP) kinase quantification, and H&E staining was performed on colonic tissues. Mucosa-associated microbiota composition was characterized by 16S ribosomal RNA sequencing. For the in vitro experiments, murine intestinal crypts and the human mucus-secreting HT29-methotrexate treated cell line were stimulated with MDX in the presence or absence of TUDCA or a p38 MAP kinase inhibitor.ResultsDiets enriched in MDX, but not propylene glycol or animal gelatin, exacerbated intestinal inflammation in both models. Analysis of the mechanisms underlying the detrimental effect of MDX showed up-regulation of inositol requiring protein 1β, a sensor of ER stress, in goblet cells, and a reduction of mucin-2 expression with no significant change in mucosa-associated microbiota. Stimulation of murine intestinal crypts and HT29-methotrexate treated cell line cells with MDX induced inositol requiring protein 1β via a p38 MAP kinase–dependent mechanism. Treatment of mice with TUDCA prevented mucin-2 depletion and attenuated colitis in MDX-fed mice.ConclusionsMDX increases ER stress in gut epithelial cells with the downstream effect of reducing mucus production and enhancing colitis susceptibility.

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Section: Discussionmentioning

confidence: 99%

The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress–Driven Mucus Depletion and Exacerbates Intestinal Inflammation

Laudisi

Fusco

Dinallo

et al. 2019

Cellular and Molecular Gastroenterology and Hepatology

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“…The number of polarized M1 macrophages peaks at one week after injury and exacerbates neuroinflammation by secreting inflammatory cytokines such as TNF-α and IL-6 (Ko et al , 2017). On the other hand, polarized M2 macrophages induce anti-inflammatory cytokines and growth factors (Kim et al , 2018). As shown in Fig 5, D-GSH significantly decreased inflammatory cytokines.…”

Section: Resultsmentioning

confidence: 99%

Chirality-dependent anti-inflammatory effect of glutathione after spinal cord injury

Kim

Han

et al. 2020

Preprint

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Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared to that in L-GSH-treated rats (***p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared to those outcomes in L-GSH-treated rats (**p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial scar via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared to L-GSH (***p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (***p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases.

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“…In the present study, we did not evaluate the effect of TUDCA on inflammatory reaction. It is well known that TUDCA has a powerful anti-inflammatory effect [ 24 ]. Human and animal experiments showed pro-inflammatory cytokines as primary mediators of the accelerated bone loss at post-menopause including interleukin-1, tumor necrosis factor-alpha, and interleukin-6.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, in our OVX-induced osteoporosis mice model, the distal femur was chosen to analyze the effect of TUDCA on OVX-induced osteoporosis. BMD is considered an important indicator that reflects bone metabolism status and is widely used to analyze changes in bone mass and predict fracture risk [ 1 , 2 , 3 , 4 , 18 , 24 ]. In addition, the levels of PINP and CTX are commonly used as biochemical markers for bone resorption and formation, respectively [ 1 , 2 , 3 , 4 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis

Ahn

Kim

Joshi

et al. 2020

IJMS

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Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteoporosis. Following treatment with different concentrations of TUDCA, cell viability, differentiation, and mineralization were measured. Three-month-old female C57BL/6 mice were randomly divided into three groups (n = 8 mice per group): (i) normal mice as the control group, (ii) ovariectomy (OVX) group (receiving phosphate-buffered saline (PBS) treatment every other day for 4 weeks), and (iii) OVX group with TUDCA (receiving TUDCA treatment every other day for 4 weeks starting 6 weeks after OVX). At 11 weeks post-surgery, serum levels of procollagen type I N-terminal propeptides (PINP) and type I collagen crosslinked C-telopeptides (CTX) were measured, and all mice were sacrificed to examine the distal femur by micro-computed tomography (CT) scans and histology. TUDCA (100 nM, 1 µM) significantly increased the proliferation and viability of osteoblasts and osteoblast differentiation and mineralization when used in vitro. Furthermore, TUDCA neutralized the detrimental effects of methylprednisolone (methylprednisolone-induced osteoblast apoptosis). In the TUDCA treatment group the PINP level was higher and the CTX level was lower, but these levels were not significantly different compared to the PBS treatment group. Micro-CT and histology showed that the TUDCA treatment group preserved more trabecular structures in the distal femur compared to the PBS treatment group. In addition, the TUDCA treatment group increased the percentage bone volume with respect to the total bone volume, bone mineral density, and mice distal femur trabeculae compared with the PBS treatment group. Taken together, our findings suggest that TUDCA may provide a favorable effect on bones and could be used for the prevention and treatment of osteoporosis.

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Anti-inflammatory effect of Tauroursodeoxycholic acid in RAW 264.7 macrophages, Bone marrow-derived macrophages, BV2 microglial cells, and spinal cord injury

Cited by 38 publications

References 32 publications

The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress–Driven Mucus Depletion and Exacerbates Intestinal Inflammation

The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress–Driven Mucus Depletion and Exacerbates Intestinal Inflammation

Chirality-dependent anti-inflammatory effect of glutathione after spinal cord injury

Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis

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