Inhibition of Intestinal Epithelial Apoptosis Improves Survival in a Murine Model of Radiation Combined Injury

Jung, Enjae; Perrone, Erin E.; Brahmamdan, Pavan; McDonough, Jacquelyn S.; Leathersich, Ann; Dominguez, Jessica A.; Fox, Amy; Dunne, William M.; Hotchkiss, Richard S.; Coopersmith, Craig M.

doi:10.1371/journal.pone.0077203

Cited by 10 publications

(8 citation statements)

References 41 publications

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“…CSF 3 receptor is the primary high-affinity receptor for G-CSF and uses the Janus kinase/signal transducer and activator of transcription and V-Yes-1 Yamaguchi Sarcoma Viral Related Oncogene Homolog signal transduction pathways. 36 , 37 , 38 , 39 Furthermore, SOCS3, BCL2A1, and CXCR2 are induced in response to G-CSF activity. G-CSF pathway activation includes dendritic cell differentiation, neutrophil mobilization, and, more generally, cell survival.…”

Section: Discussionmentioning

confidence: 99%

Environmental Enteric Dysfunction Includes a Broad Spectrum of Inflammatory Responses and Epithelial Repair Processes

Ordiz

Stauber

et al. 2016

Cellular and Molecular Gastroenterology and Hepatology

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Background & AimsEnvironmental enteric dysfunction (EED), a chronic diffuse inflammation of the small intestine, is associated with stunting in children in the developing world. The pathobiology of EED is poorly understood because of the lack of a method to elucidate the host response. This study tested a novel microarray method to overcome limitation of RNA sequencing to interrogate the host transcriptome in feces in Malawian children with EED.MethodsIn 259 children, EED was measured by lactulose permeability (%L). After isolating low copy numbers of host messenger RNA, the transcriptome was reliably and reproducibly profiled, validated by polymerase chain reaction. Messenger RNA copy number then was correlated with %L and differential expression in EED. The transcripts identified were mapped to biological pathways and processes. The children studied had a range of %L values, consistent with a spectrum of EED from none to severe.ResultsWe identified 12 transcripts associated with the severity of EED, including chemokines that stimulate T-cell proliferation, Fc fragments of multiple immunoglobulin families, interferon-induced proteins, activators of neutrophils and B cells, and mediators that dampen cellular responses to hormones. EED-associated transcripts mapped to pathways related to cell adhesion, and responses to a broad spectrum of viral, bacterial, and parasitic microbes. Several mucins, regulatory factors, and protein kinases associated with the maintenance of the mucous layer were expressed less in children with EED than in normal children.ConclusionsEED represents the activation of diverse elements of the immune system and is associated with widespread intestinal barrier disruption. Differentially expressed transcripts, appropriately enumerated, should be explored as potential biomarkers.

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Section: Discussionmentioning

confidence: 99%

Environmental Enteric Dysfunction Includes a Broad Spectrum of Inflammatory Responses and Epithelial Repair Processes

Ordiz

Stauber

et al. 2016

Cellular and Molecular Gastroenterology and Hepatology

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“…Currently, there are no readily available pharmacological agents that offer effective mitigation of RIGS, and as such there is great interest in developing such mitigators. 1 - 3 For clinical radiation therapy of thoracic, abdominal, and genitourinary cancers, the collateral irradiation of abdominal tissue is often dose limiting.…”

Section: Introductionmentioning

confidence: 99%

“…4 Much of the current knowledge about RIGS comes from small animal models mainly utilizing mice. [1][2][3]5,6 As the Food and Drug Administration requires the effect of radiation mitigators to be proven in separate animal models, studies have also been conducted using nonhuman primates and minipigs. [7][8][9] Death from HS occurs at lower radiation doses compared to RIGS, so partial bone marrow shielding is needed to investigate the long-term (>20 days) efficacy of mitigators for acute abdominal toxicity.…”

Section: Introductionmentioning

confidence: 99%

A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems

2017

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Background and Purpose:Currently, no readily available mitigators exist for acute abdominal radiation injury. Here, we present an animal model for precise and homogenous limb-sparing abdominal irradiation (LSAIR) to study the radiation-induced gastrointestinal syndrome (RIGS).Materials and Methods:The LSAIR technique was developed using the small animal radiation research platform (SARRP) with image guidance capabilities. We delivered LSAIR at doses between 14 and 18 Gy on 8- to 10-week-old male C57BL/6 mice. Histological analysis was performed to confirm that the observed mortality was due to acute abdominal radiation injury.Results:A steep dose–response relationship was found for survival, with no deaths seen at doses below 16 Gy and 100% mortality at above 17 Gy. All deaths occurred between 6 and 10 days after irradiation, consistent with the onset of RIGS. This was further confirmed by histological analysis showing clear differences in the number of regenerative intestinal crypts between animals receiving sublethal (14 Gy) and 100% lethal (18 Gy) radiation.Conclusion:The developed LSAIR technique provides uniform dose delivery with a clear dose response, consistent with acute abdominal radiation injury on histological examination. This model can provide a useful tool for researchers investigating the development of mitigators for accidental or clinical high-dose abdominal irradiation.

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“…20 Immune cell populations respond differently depending upon which compartment they are in. 21 In studies combining radiotherapy and immunotherapy, NK cells sensitize the tumor cells to radiation and the radiation sensitizes the tumor cells to NK cell attack. 22 It was also observed that CD244.2 mediates NK/NKT-like cell activation with its mediated signaling contributing both positively and negatively to viral clearance and immune mediated diseases.…”

Section: Discussionmentioning

confidence: 99%

Radiation Response of Circulating SLAM Markers in Mice Treated with Papaya Leaf Extract and Diallyl Disulfide

Somayaji¹,

Vasudeva²,

Shetty³

et al. 2019

JYP

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Background: CD48, CD150 and CD244.2 are the signaling lymphocytic activation molecules (SLAM) of hematopoietic population expressed on the T cells, B cells, monocytes, macrophages and play an important role in adaptive immune response. Aim: The present study aims at evaluating the individual circulating levels of these SLAM markers in response to electron beam radiation and the protective effects of Carica papaya (L.) and DADS intervention. Methods and Material: The mice were fed orally with 100mg/kg body weight of papaya leaf extract and 10mg/kg body weight of DADS. The extract and DADS were administered to individual groups for 5 consecutive days with respective control groups and exposed to 6Gy of electrons radiation. Results: The present study indicated significant rise in the CD244.2 levels in irradiation control and a near normal levels in groups with C.papaya and DADS intervention. A significant decrease in the CD48 expression of granulocytes is seen in radiation control group on comparison to the normal control group. A significant rise is seen in the CD48 expression of granulocytes with DADS treatment prior irradiation when compared to DADS control. A significant increase in the granulocyte CD150 expression with DADS treatment prior irradiation group is seen when compared to the DADS control group. In DADS treatment prior irradiation compared to radiation control the CD244.2 expression in granulocytes is significantly lowered. Conclusion: Study suggests a potential increase in the percentage of CD244.2 + lymphocytes in response to electron beam radiation and a comparative decrease in the percentage of CD244.2 + lymphocytes in C.papaya leaf extract and DADS intervention.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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Inhibition of Intestinal Epithelial Apoptosis Improves Survival in a Murine Model of Radiation Combined Injury

Cited by 10 publications

References 41 publications

Environmental Enteric Dysfunction Includes a Broad Spectrum of Inflammatory Responses and Epithelial Repair Processes

Environmental Enteric Dysfunction Includes a Broad Spectrum of Inflammatory Responses and Epithelial Repair Processes

A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems

Radiation Response of Circulating SLAM Markers in Mice Treated with Papaya Leaf Extract and Diallyl Disulfide

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