Background: Elevated expression of the proinflammatory cytokine interleukin 1β (IL-1β) has been observed in expressed prostatic secretions of patients with chronic prostatitis/chronic pelvic pain syndrome, and genetic polymorphisms associated with the IL1B gene are linked to increased risk for aggressive prostate cancer.
Methods:To study the role of IL-1β expression in prostate inflammation, we examined IL1B expression in human prostatic proliferative inflammatory atrophy (PIA) lesions and developed a tetracycline-regulated human IL1B transgene in the mouse prostate.Results: Here, we demonstrate that IL1B expression is a common finding in human PIA lesions, which harbored focal IL1B expression in epithelial and stromal compartments. Human IL1B expression in the mouse prostate elicited acute and chronic inflammation. Penetrance and expressivity were variable and tunable by altering transgene dosage and the presence of an exogenous inducible marker antigen (green fluorescent protein). Inflammation was characterized by infiltration of CD4 + T cells, demonstrating an adaptive immune response. Chronic inflammation persisted after doxycycline (Dox) withdrawal. Reactive epithelia increased expression of downstream cytokines, and altered glandular architecture was observed upon sustained induction of IL1B. Immunohistochemical analyses revealed a higher proliferative index and decreased Nkx3.1 expression in inflamed mouse prostates. Conclusions: These data implicate IL-1β in human prostate pathology and this model provides a versatile platform to interrogate molecular mechanisms of inflammationassociated prostate pathologies associated with episodic or sustained IL-1β expression. K E Y W O R D S interleukin 1β, mouse model, proliferative inflammatory atrophy, prostate inflammation The Prostate. 2019;79:732-745. wileyonlinelibrary.com/journal/pros 732 |
Previous models suggested that regulation of telomere length in Saccharomyces cerevisiae by Tel1(ATM) and Mec1(ATR) would parallel the established pathways regulating the DNA damage response. Here, we provide evidence that telomere length regulation differs from the DNA damage response in both the Tel1 and Mec1 pathways. We found that Rad53 mediates a Mec1 telomere length regulation pathway but is dispensable for Tel1 telomere length regulation, whereas in the DNA damage response, Rad53 is regulated by both Mec1 and Tel1. Using epistasis analysis with a Tel1 hypermorphic allele, Tel1-hy909, we found that the MRX complex is not required downstream of Tel1 for telomere elongation but is required downstream of Tel1 for the DNA damage response. Our data suggest that nucleolytic telomere end processing is not a required step for telomerase to elongate telomeres.
SUMMARY
Investigation of the anthocyan skin pigments in hands 1, 2, and 3 isolated from Vitis vinifera var. Tinta Pinheira grapes showed that the pigments from hand 2 consisted of the 3‐mono‐glucosides of malvidin, peonidin, delphinidin, and petunidin, each acylated with p‐coumaric acid. The pigments from hand 3 consisted of the same four anthocyanins, each acylated with caffeic acid. Evidence is presented to show that the pigments in hand 1 were an artifact obtained under certain experimental conditions, and a tentative explanation for their formation is proposed.
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