White button mushroom interrupts tissue AR-mediated TMPRSS2 expression and attenuates pro-inflammatory cytokines in C57BL/6 mice

White button mushroom (WBM) is a common edible mushroom consumed in the United States and many European and Asia-Pacific countries. We previously reported that dietary WBM antagonized dihydrotestosterone (DHT)-induced androgen receptor (AR) activation and reduced myeloid-derived suppressor cells (MDSCs) in prostate cancer animal models and patients. Transmembrane protease serine 2 (TMPRSS2), an androgen-induced protease in prostate cancer, has been implicated in influenza and coronavirus entry into the host cell, triggering host immune response. The present study on C57BL/6 mice revealed that WBM is a unique functional food that (A) interrupts AR-mediated TMPRSS2 expression in prostate, lungs, small intestine, and kidneys through its AR antagonistic activity and (B) attenuates serum pro-inflammatory cytokines and reduces MDSC counts through its immunoregulatory activity. These findings provide a scientific basis for translational studies toward clinical applications of WBM in diseases related to TMPRSS2 expression and immune dysregulation.


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Sample size
To study WBM-mediated AR-TMPRSS2 suppression, 12 mice were randomly divided into 4 groups (n=3 each group); To study WBM-mediated immunomodulation, 15 mice were randomly divided into 3 groups (n=5 each group); For the expression of AR, TMPRSS2, and ACE2 in the human prostate, lungs, small intestine, and kidneys, the mRNA expression values were obtained from "The Human Protein Atlas/HPA" (http://www.proteinatlas.org/). There were 152 samples for prostate, 427 samples for lungs, 137 samples for the small intestine, and 45 samples for kidneys.
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We require information from authors about some types of materials, experimental systems and methods used in many studies. Here, indicate whether each material, system or method listed is relevant to your study. If you are not sure if a list item applies to your research, read the appropriate section before selecting a response. Field-collected samples Mice were housed in an AAALAC (Association for Assessment and Accreditation of Laboratory Animal Care International)-accredited Animal Resources Center. Throughout the treatments, body weights were monitored every two days as an indicator of the mice's overall health. At the end of the treatments, the mice were euthanized. The prostate, lungs, small intestine, and kidneys were flashfrozen in liquid nitrogen and/or fixed with 4% paraformaldehyde. Whole blood samples were collected and isolated into serum and cell pellets. Serum samples were stored at −80°C for the cytokine array assay, while cell pellets were pre-fixed and stored at −80°C for the flow cytometry assay. Spleens were collected to isolate splenocytes, which were then pre-fixed and stored at −80°C for the flow cytometry assay.

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Animal research procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at City of Hope (Approval Number:, 15051) Note that full information on the approval of the study protocol must also be provided in the manuscript.

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Sample preparation
Whole blood samples were collected and isolated into serum and cell pellets. Serum samples were stored at −80°C for the cytokine array assay, while cell pellets were pre-fixed and stored at −80°C for the flow cytometry assay. Spleens were collected to isolate splenocytes, which were then pre-fixed and stored at −80°C for the flow cytometry assay.