Reduced intestinal inflammation induced by dextran sodium sulfate in interleukin-6-deficient mice

Although several studies have revealed the role of different lipid mediators in colitis, the comprehensive analysis of their production across different phases of colitis remained unclear. Here, we performed the following analysis in the dextran sodium sulfate (DSS)-induced colitis model using LC-MS/MS. Oral administration of 2% DSS in mice for 4 days resulted in severe intestinal inflammation by day 7, which gradually subsided by day 18. Based on the disease scoring index (assigned on the basis of fecal condition and weight loss), we defined the phases of colitis as induction (days 0–4), acute inflammation (days 4–7), recovery (days 7–9), and late recovery (days 9–18). Across all phases, 58 lipid mediators were detected in the inflamed colon tissue. In the induction phase, the production of n-6 fatty acid-derived prostaglandin E2 and thromboxane B2 increased by ∼2-fold. In the acute inflammation phase, the production of n-6 fatty acid-derived leukotrienes increased by >10-fold, while that of n-3 fatty acid-derived hydroxyeicosapentaenoic acids and dihydroxyeicosatetraenoic acids decreased. In the recovery phase, a precursor of protectin D1 (17-hydroxydocosahexaenoic acid) increased over 3-fold. These observations suggested dynamic changes in the production of lipid mediators across different phases of the disease and their potential regulation in healing colitis.

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Malt1 blocks IL-1β production by macrophages in vitro and limits dextran sodium sulfate-induced intestinal inflammation in vivo

Journal of Leukocyte Biology ◽

10.1002/jlb.3vma0118-019r ◽

2018 ◽

Vol 104 (3) ◽

pp. 557-572 ◽

Cited By ~ 2

Author(s):

Mahdis Monajemi ◽

Yvonne C. F. Pang ◽

Saelin Bjornson ◽

Susan C. Menzies ◽

Nico van Rooijen ◽

...

Keyword(s):

Sodium Sulfate ◽

Intestinal Inflammation ◽

Dextran Sodium Sulfate

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Interleukin-6, but not the interleukin-6 receptor plays a role in recovery from dextran sodium sulfate-induced colitis

International Journal of Molecular Medicine ◽

10.3892/ijmm.2014.1825 ◽

2014 ◽

Vol 34 (3) ◽

pp. 651-660 ◽

Cited By ~ 28

Author(s):

JAN SOMMER ◽

ERIKA ENGELOWSKI ◽

PAUL BARAN ◽

CHRISTOPH GARBERS ◽

DOREEN M. FLOSS ◽

...

Keyword(s):

Interleukin 6 ◽

Sodium Sulfate ◽

Dextran Sodium Sulfate ◽

Interleukin 6 Receptor

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Interleukin-10 is Differentially Expressed in the Small Intestine and the Colon Experiencing Chronic Inflammation and Ulcerative Colitis Induced by Dextran Sodium Sulfate in Young Pigs

Physiological Research ◽

10.33549/physiolres.933259 ◽

2017 ◽

pp. 147-162 ◽

Cited By ~ 5

Author(s):

D. LACKEYRAM ◽

D. YOUNG ◽

C. J. KIM ◽

C. YANG ◽

T. L. ARCHBOLD ◽

...

Keyword(s):

Ulcerative Colitis ◽

Chronic Inflammation ◽

Chronic Ulcerative Colitis ◽

Sodium Sulfate ◽

Intestinal Inflammation ◽

Interleukin 10 ◽

Dextran Sodium Sulfate ◽

Mrna Abundance ◽

Control Group ◽

Young Pigs

Intestinal inflammation induced with dextran sodium sulfate (DSS) is used to study acute or chronic ulcerative colitis in animal models. Decreased gut tissue anti-inflammatory cytokine IL-10 concentration and mRNA abundance are associated with the development of chronic bowel inflammation. Twelve piglets of 3 days old were fitted with an intragastric catheter and randomly allocated into control and DSS groups by administrating either sterile saline or 1.25 g of DSS/kg body weight (BW) in saline per day, respectively, for 10 days. Growth rate and food conversion efficiency were reduced (p<0.05) in the DSS piglets compared with the control group. Quantitative histopathological grading of inflammation in the jejunum and colon collectively showed that the DSS treatment resulted in 12 fold greater (p<0.05) inflammation severity scoring in the colon than in the jejunum, indicative of chronic ulcerative colitis in the colon. Upper gut permeability endpoint was 27.4 fold higher (p<0.05) in the DSS group compared with the control group. The DSS group had higher concentrations and mRNA abundances (p<0.05) of TNF- and IL-6 in the jejunal and colonic tissues compared with the control group. Colonic concentration and mRNA abundance of IL-10 were reduced (p<0.05), however, jejunal IL-10 mRNA abundance was increased (p<0.05) in the DSS group compared with the control group. In conclusion, administration of DSS at 1.25 g/kg BW for 10 days respectively induced acute inflammation in the jejunum and chronic inflammation and ulcerative colitis in the colon with substantially decreased colonic concentration and mRNA abundance of IL-10 in the young pigs, mimicking the IL-10 expression pattern in humans associated with chronic bowel inflammation.

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Lactobacillus bulgaricus inhibits colitis-associated cancer via a negative regulation of intestinal inflammation in azoxymethane/dextran sodium sulfate model

World Journal of Gastroenterology ◽

10.3748/wjg.v26.i43.6782 ◽

2020 ◽

Vol 26 (43) ◽

pp. 6782-6794

Author(s):

Denise Sayuri Calheiros Silveira ◽

Luciana Chain Veronez ◽

Luís Carlos Lopes-Júnior ◽

Elen Anatriello ◽

Mariângela Ottoboni Brunaldi ◽

...

Keyword(s):

Sodium Sulfate ◽

Intestinal Inflammation ◽

Negative Regulation ◽

Dextran Sodium Sulfate ◽

Lactobacillus Bulgaricus

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Intervention of Isomaltodextrin Mitigates Intestinal Inflammation in a Dextran Sodium Sulfate-Induced Mouse Model of Colitis via Inhibition of Toll-like Receptor-4

Journal of Agricultural and Food Chemistry ◽

10.1021/acs.jafc.6b04903 ◽

2017 ◽

Vol 65 (4) ◽

pp. 810-817 ◽

Cited By ~ 12

Author(s):

Kaustav Majumder ◽

Toshihiko Fukuda ◽

Hua Zhang ◽

Takeo Sakurai ◽

Yoshifumi Taniguchi ◽

...

Keyword(s):

Mouse Model ◽

Sodium Sulfate ◽

Intestinal Inflammation ◽

Dextran Sodium Sulfate ◽

Toll Like Receptor ◽

Toll Like Receptor 4

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Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1808426115 ◽

2018 ◽

Vol 115 (33) ◽

pp. 8418-8423 ◽

Cited By ~ 15

Author(s):

Hisako Kayama ◽

Masako Kohyama ◽

Daisuke Okuzaki ◽

Daisuke Motooka ◽

Soumik Barman ◽

...

Keyword(s):

Sodium Sulfate ◽

Intestinal Inflammation ◽

Local Environment ◽

Dextran Sodium Sulfate ◽

Dependent Manner ◽

Tnf Α ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Mucosal Bleeding ◽

Inducible Genes

The local environment is crucial for shaping the identities of tissue-resident macrophages (Mϕs). When hemorrhage occurs in damaged tissues, hemoglobin induces differentiation of anti-inflammatory Mϕs with reparative function. Mucosal bleeding is one of the pathological features of inflammatory bowel diseases. However, the heme-mediated mechanism modulating activation of intestinal innate immune cells remains poorly understood. Here, we show that heme regulates gut homeostasis through induction of Spi-C in intestinal CX3CR1high Mϕs. Intestinal CX3CR1high Mϕs highly expressed Spi-C in a heme-dependent manner, and myeloid lineage-specific Spic-deficient (Lyz2-cre; Spicflox/flox) mice showed severe intestinal inflammation with an increased number of Th17 cells during dextran sodium sulfate-induced colitis. Spi-C down-regulated the expression of a subset of Toll-like receptor (TLR)-inducible genes in intestinal CX3CR1high Mϕs to prevent colitis. LPS-induced production of IL-6 and IL-1α, but not IL-10 and TNF-α, by large intestinal Mϕs from Lyz2-cre; Spicflox/flox mice was markedly enhanced. The interaction of Spi-C with IRF5 was linked to disruption of the IRF5-NF-κB p65 complex formation, thereby abrogating recruitment of IRF5 and NF-κB p65 to the Il6 and Il1a promoters. Collectively, these results demonstrate that heme-mediated Spi-C is a key molecule for the noninflammatory signature of intestinal Mϕs by suppressing the induction of a subset of TLR-inducible genes through binding to IRF5.

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