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

Abstract

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.

Beta-Glucans from Fungi: Biological and Health-Promoting Potential in the COVID-19 Pandemic Era

“…Immunomodulatory, antioxidant, neuroprotective, and antithrombotic activities are of particular interest here. There are still few studies on the use of β-glucans from edible mushrooms for COVID-19 [14,175]. Edible macrofungi appear to be an excellent source of β-glucans for clinical applications, due in part to the lack of toxicological risk from fungal toxins.…”

“…Beta-glucan-induced DC cells present the virus more efficiently to T lymphocytes, which promotes stimulation of B lymphocytes and antibody production. Thus, beta-glucans may favorably influence the development of a long-term, specific, adaptive response to SARS-CoV-2 [172,175].…”

“…[ 169,177,191] The promising results of studies on mushroom β-glucan from Agaricus bisporus and Lentinula edodes [14,175] allow us to assume a beneficial effect of these compounds in the prevention, course, and counteracting complications of COVID-19 in the era of the pandemic caused by SARS-CoV-2. Still, there are only a few studies on the promising function of mushroom β-glucans in the context of COVID-19; such research needs to be continued due to the easy availability and significant amounts of beta-glucans in mushrooms [35], as well as the safety and ease of administration without significant side effects, even in the case of insufficient purification [14,186,187].…”

Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature, Informatics, and Inspiration from the Dog

“…Unlike the Pseudomonas/ACE2 case, however, it seems unlikely that the capacity of Moraxella bacteria to modulate TMPRSS2 action arises from direct influ-ence on expression. Rather, the most readily measurable TMPRSS2-mediated influence of commensal bacteria seems to entail suppression of the enzyme's activity, not abundance, as evinced by changes in TMPRSS2-triggered pathways, including the immunological interferon antiviral response [175,217], and downstream androgen-mediated angiogenic effects [181,182,218,219]. This implies that any prospective TMPRSS2-related benefit arising from an elevated Moraxella fraction may be attributed to effects that diminish the rate of viral Spike protein cleavage relative to basal TMPRSS2 action.…”