Role of IL-17RA in the proliferative priming of hepatocytes in liver regeneration

Abstract

A tight link has been established between inflammation and cancer. Liver regeneration is a widely used model to study the correlation between inflammation and proliferation. IL-6 is essentially involved in liver regeneration and in cancer. Recently, IL-17A has been shown to regulate not only inflammation, but also cell proliferation. Here, we analyze the role played by IL-17A signaling in liver regeneration by comparing cell proliferation in Wild Type and IL-17RA −/− mice. Partial hepatectomy experiments performed in IL-17RA −/− mice showed a delay in expression of earlygenes to prime the residual hepatocyte to proliferate, with subsequent delay in G 1 /S-phase transition. We demonstrated that IL-17RA regulates, by recruitment of non-parenchymal cell, the expression of IL-6, which in turn triggers the proliferation of residual hepatocytes. Our data indicate an important role played by IL-17RA in liver proliferation via IL-6. ARTICLE HISTORY

HOPS/TMUB1 retains p53 in the cytoplasm and sustains p53‐dependent mitochondrial apoptosis

“…Compound (Sakura â Finetek, Torrance, CA) for cryosection procedure (5 lm tissue slide) or washed in ice-cold phosphate-buffered saline (PBS) 1× (Sigma-Aldrich, St. Louis, MO) and quickly processed for subcellular fractionation [49]. No randomization and no blinding of the investigators were used for the experiments on animals.…”

Secukinumab attenuates reactive astrogliosis via IL‐17RA/(C/EBPβ)/SIRT1 pathway in a rat model of germinal matrix hemorrhage

“…IL‐17A, secreted by immune cells, plays a vital role in the stroke pathophysiology. In addition to its pro‐inflammatory effect, IL‐17A has been shown to promote hyperproliferation and differentiation of various cell types; the most notable are Th17 cells and γδT cells due to their production of IL‐17A . After hemorrhagic stroke, macrophages become activated and secret IL‐23, which promotes the activation of γδT cells and Th cells .…”

“…In addition to its pro-inflammatory effect, IL-17A has been shown to promote hyperproliferation and differentiation of various cell types; the most notable are Th17 cells and γδT cells due to their production of IL-17A. 17,[45][46][47][48] After hemorrhagic stroke, macrophages become activated and secret IL-23, which promotes the activation of γδT cells and Th cells. 18 Due to the blood-brain barrier (BBB) rupture after hemorrhagic stroke, 49 IL-17A enters into the brain tissue through the serum.…”

The two facets of gp130 signalling in liver tumorigenesis

“…Under these conditions, myeloid cells, in particular, KCs are the major source of IL-6 and OSM. However, it was also demonstrated that non-parenchymal cells recruited via IL-17 are important sources of IL-6 during liver regeneration [16] and hepatic fibrosis [17]. During chronic liver disease also senescent hepatocytes and BECs secrete IL-6 (see also below), while OSM is also secreted by hepatic progenitor cells [18].…”