Interleukin-17A plays a pivotal role after partial hepatectomy in mice

Abstract

Background: Liver regeneration after partial hepatectomy (PH) is regulated by tumor necrosis factor (TNF)-α derived from the Kupffer cell. Furthermore, it was reported from our laboratory that interleukin (IL)-17A enhances the production of TNF-α by the Kupffer cell, suggesting that IL-17A may play a role in liver regeneration.

Objective: The purpose was to determine the role of IL-17A and the spleen in liver regeneration after PH.

Methods: Two mouse models including the wild-type (WT) mice or the IL-17A knockout (KO) mice underwent PH. Animals were killed at the designated time points; liver tissues were harvested for further investigation. Proliferation of hepatocytes was evaluated. Furthermore, the messenger RNA and protein expression of TNF-α and IL-6 were measured in the liver. In another set of experiments, the two animal models underwent splenectomy before PH. In an in vitro study, CD4-positive lymphocytes in the spleen were isolated from mice, and the number of IL-17A-positive cells was investigated.

Results: Liver regeneration was significantly impaired in the KO mice compared with the WT mice. This was associated with suppression of cell proliferation assessed by cell proliferation markers in the KO mice. In the WT mice that underwent splenectomy, liver regeneration was significantly delayed compared with animals without splenectomy. In contrast, splenectomy did not affect liver regeneration in the KO mice. IL-17A-positive lymphocytes increased significantly in the spleen in the WT mice after PH.

Conclusions: These results indicate that IL-17A derived from CD4-positive lymphocytes in the spleen is a key regulator in liver regeneration after PH.

Keywords: Cytokine; Interleukin-17A; Interleukin-17A knockout mouse; Kupffer cell; Partial hepatectomy; Spleen; Splenectomy.