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

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. PMID: 32035059 [PubMed - as supplied by publisher]
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research