Abstract
In patients with active brucellosis, the liver is frequently affected by histopathologic lesions, such as granulomas, inflammatory infiltrations, and parenchymal necrosis. Herein, we examine some potential mechanisms of liver damage in brucellosis. We demonstrate that Brucella abortus infection inhibits matrix metalloproteinase-9 (MMP-9) secretion and induces collagen deposition and tissue inhibitor of matrix metalloproteinase-1 secretion induced by hepatic stellate cells (LX-2). These phenomena depend on transforming growth factor-β1 induction. In contrast, supernatants from B. abortus-infected hepatocytes and monocytes induce MMP-9 secretion and inhibit collagen deposition in hepatic stellate cells. Yet, if LX-2 cells are infected with B. abortus, the capacity of supernatants from B. abortus-infected hepatocytes and monocytes to induce MMP-9 secretion and inhibit collagen deposition is abrogated. These results indicate that depending on the balance between interacting cells and cytokines of the surrounding milieu, the response of LX-2 cells could be turned into an inflammatory or fibrogenic phenotype. Livers from mice infected with B. abortus displayed a fibrogenic phenotype with patches of collagen deposition and transforming growth factor-β1 induction. This study provides potential mechanisms of liver immune response induced by B. abortus-infected hepatic stellate cells. In addition, these results demonstrate that the cross talk of these cells with hepatocytes and macrophages implements a series of interactions that may contribute to explaining some of mechanisms of liver damage observed in human brucellosis.
Highlights
In patients with active brucellosis, the liver is frequently affected by histopathologic lesions, such as granulomas, inflammatory infiltrations, and parenchymal necrosis
Because we previously demonstrated that hepatocytes could be infected by B. abortus and that this infection elicited the secretion of cytokines,[7] we decided to investigate whether supernatants from B. abortuseinfected hepatocytes induced matrix metalloproteinase-9 (MMP-9) secretion by LX-2 cells
The increase in matrix metalloproteinases (MMPs)-9 secretion by LX-2 cells induced by supernatants from B. abortuseinfected hepatocytes and monocytes is in correlation with an inhibition in collagen deposition as determined by Sirius red staining (Figure 5, E and F). These results indicate that supernatants from B. abortuseinfected monocytes and hepatocytes induced MMP-9 secretion and inhibited collagen deposition by LX-2 cells
Summary
In patients with active brucellosis, the liver is frequently affected by histopathologic lesions, such as granulomas, inflammatory infiltrations, and parenchymal necrosis. We demonstrate that Brucella abortus infection inhibits matrix metalloproteinase-9 (MMP-9) secretion and induces collagen deposition and tissue inhibitor of matrix metalloproteinase-1 secretion induced by hepatic stellate cells (LX-2) These phenomena depend on transforming growth factor-b1 induction. If LX-2 cells are infected with B. abortus, the capacity of supernatants from B. abortuseinfected hepatocytes and monocytes to induce MMP-9 secretion and inhibit collagen deposition is abrogated These results indicate that depending on the balance between interacting cells and cytokines of the surrounding milieu, the response of LX-2 cells could be turned into an inflammatory or fibrogenic phenotype. This study provides potential mechanisms of liver immune response induced by B. abortuseinfected hepatic stellate cells These results demonstrate that the cross talk of these cells with hepatocytes and macrophages implements a series of interactions that may contribute to explaining some of mechanisms of liver damage observed in human brucellosis. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript
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