The NR4A agonist, Cytosporone B, attenuates pro-inflammatory mediators in human colorectal cancer tissue ex vivo
Autor: | Sarah Aldhafiri, K. Thornton, Des C. Winter, Eoin P. Cummins, Brenda Murphy, Mohamed Ismaiel, Hugh E. Giffney, Anindya Mukhopadhya, Sarinj Fattah, Ciara E. Keogh, Helen Mohan, Daniel Crean, Evelyn P. Murphy |
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Rok vydání: | 2021 |
Předmět: |
Agonist
Adult Male Chemokine medicine.drug_class Colorectal cancer medicine.medical_treatment Biophysics Inflammation Biochemistry medicine Nuclear Receptor Subfamily 4 Group A Member 1 Humans Receptor Molecular Biology Aged Phenylacetates Aged 80 and over biology business.industry Cell Biology Middle Aged medicine.disease Cytokine biology.protein Cancer research Cytokines Tumor necrosis factor alpha Female medicine.symptom Chemokines Inflammation Mediators business Colorectal Neoplasms Ex vivo |
Zdroj: | Biochemical and biophysical research communications. 554 |
ISSN: | 1090-2104 |
Popis: | Inflammation is a pivotal pathological factor in colorectal cancer (CRC) initiation and progression, and modulating this inflammatory state has the potential to ameliorate disease progression. NR4A receptors have emerged as key regulators of inflammatory pathways that are important in CRC. Here, we have examined the effect of NR4A agonist, Cytosporone B (CsnB), on colorectal tissue integrity and its effect on the inflammatory profile in CRC tissue ex vivo. Here, we demonstrate concentrations up 100 μM CsnB did not adversely affect tissue integrity as measured using transepithelial electrical resistance, histology and crypt height. Subsequently, we reveal through the use of a cytokine/chemokine array, ELISA and qRT-PCR analysis that multiple pro-inflammatory mediators were significantly increased in CRC tissue compared to control tissue, which were then attenuated with the addition of CsnB (such as IL-1β, IL-8 and TNFα). Lastly, stratification of the data revealed that CsnB especially alters the inflammatory profile of tumours derived from males who had not undergone chemoradiotherapy. Thus, this study demonstrates that NR4A agonist CsnB does not adversely affect colon tissue structure or functionality and can attenuate the pro-inflammatory state of human CRC tissue ex vivo. |
Databáze: | OpenAIRE |
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