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Papers of the Week

2020 Feb 05

Am J Pathol

A role of heme degradation pathway in shaping prostate inflammatory responses and lipid metabolism.


Lilljebjörn L V, Csizmadia E, Hedblom A, Canesin G, Kalbasi A, Li M, Kramer F, Bornfeldt KE, Wegiel B
Am J Pathol. 2020 Feb 05.
PMID: 32035059.


The molecular mechanisms of prostate inflammation, a common disease of the prostate with symptoms of pain and/or heighten immune response, are still poorly understood. In this study, we hypothesized that heme oxygenase-1 (HO-1), an enzyme responsible for degradation of heme to carbon monoxide (CO), bilirubin, and iron is an important regulator of inflammation and epithelial responses in the prostate. Injection of non-uropathogenic E. coli (MG1655 strain) or PBS into the urethra of mice led to increased numbers of CD45+ leukocytes and mitotic markers (phosphorylated histone H3 and phosphorylated extracellular signal-regulated kinase; Erk1/2) in the prostate glands. Leukocyte infiltration was elevated in prostates harvested from mice lacking HO-1 in the myeloid compartment. Conversely, exogenous CO (250 ppm) increased IL-1β levels and suppressed cell proliferation in the prostates. Of note, CO did not affect the number of infiltrating CD45+ cells in the prostates of either E. coli- or PBS-treated mice. Interestingly, immunomodulatory effects of HO-1 and CO correlated with early induction of the long-chain acyl-CoA synthetase 1 (ACSL1). ACSL1 was induced in response to E. coli infection in macrophages and was in part required for IL-1β expression and prostate cancer cell colony growth in soft agar. In summary, these results suggest that HO-1/CO might play a distinctive role in modulating prostate inflammation, cell proliferation and IL-1β induction in part via an ACSL1-mediated pathway.