In this installment, there’s an exciting bit of research that’s uncovered a potential therapeutic target for chronic pain in people with irritable bowel syndrome (IBS). There’s also work into calcium release-activated channels (CRAC) and resistance to SARS-CoV-2, and finally a look into how histamines help cancer cells evade immunotherapy.
Epigenetic demethylation regulates pain
Irritable bowel syndrome (IBS) doesn’t have a clear cause, but it does put a lot of people in a great deal of discomfort. Like many diseases, inflammation and injury may have a role to play and evidence already points to DNA methylation as a factor. This work from Soochow University, China, used a rat model of neonatal colonic inflammation (NCI) along with ChIP, patch-clamp and some functional assays to investigate further. Their work shows how GATA1-promoted DNA demethylation of the p2x7r locus, which occurs through physical interaction with TET3 demethylase, seems to have a regulatory impact on chronic pain in their NCI model. In addition to shedding light on the mechanisms at work, the study suggests that GATA1 and p2x7r locus-binding could well be interesting therapeutic targets for pain suppression in IBS.
Read the full paper at Neuroscience Bulletins.
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ORAI1, IFN-I, and SARS-CoV-2 resistance
We know that tonic IFN-I signaling provides a barrier to SARS-CoV 2: pretreatment of human cells with IFN-I and IFN-III or boosting IFN-I signaling both confer some resistance to SARS-CoV-2 infection. And the IFN-I response may be regulated to some degree by ORAI1 and stromal interaction molecule 1 (STIM1) – both essential to store-operated Ca2+ entry. Work from the University of California generated ORAI1 and STIM1 knockout cell lines to investigate this further. The work showed how the loss of the CRAC channel components, STIM1 and ORAI, conferred remarkable resistance to infection, revealing novel functions for these in the innate immune system.
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Antihistamines boost immunotherapy treatment
Scientists from The University of Texas MD Anderson Cancer Center have found that histamine and histamine receptor H1 (HRH1) are often in the tumor microenvironment at heightened levels and that melanoma and lung cancer patients taking H1-antihistamines during immunotherapy had significantly better clinical outcomes. It seems that cancer cells have been evading the immune system and immunotherapies via histamine. These histamine molecules, derived from cancer cells or released due to an allergy binds HRH1 on tumor-associated macrophages that suppress CD8+ T cell function. The result is faster tumor growth and increased resistance to immunotherapy.
Take a look at the data in Cancer Cell.
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Photo by Fusion Medical Animation.
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