Journal
CELLULAR IMMUNOLOGY
Volume 367, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2021.104401
Keywords
Macrophages; Endoplasmic reticulum stress; Liver fibrogenesis; Interleukin-1 alpha; ATF6
Categories
Ask authors/readers for more resources
Macrophages play a crucial role in liver fibrogenesis by producing cytokines that activate HSCs. ATF6 signaling significantly influences cytokine expression and liver fibrogenesis after acute liver injury.
Macrophages contribute to liver fibrogenesis by the production of a large variety of cytokines. ATF6 is associated with the activation of macrophages. The present study aimed to investigate the role of ATF6 in the expression of macrophage-derived cytokines and liver fibrogenesis after acute liver injury. Following thioacetamide (TAA)-induced acute liver injury, the characteristics of the occurrence of liver fibrosis and the secretion of cytokines by macrophages were first described. Then, the role of various cytokines secreted by macrophages in activating hepatic stellate cells (HSCs) was tested in vitro. Finally, endoplasmic reticulum stress (ER-stress) signals in macrophages were detected following liver injury. siRNA was used to interfere with the expression of ATF6 in macrophages to verify the influence of ATF6 on cytokine expression and liver fibrogenesis after liver injury. A single intraperitoneal injection of TAA induced acute liver injury. The depletion of macrophages attenuated acute liver injury, while it inhibited liver fibrogenesis. During acute liver injury, macrophages secrete a variety of cytokines. Most of these cytokines promoted the activation of HSCs, but the effect of IL-1 alpha was most significant. In the early stage of acute liver injury, ER-stress signals in macrophages were activated. Interference of ATF6 expression suppressed the secretion of cytokines by macrophages and attenuated liver fibrogenesis. Overall, in the early stage of acute liver injury, ATF6 signals promoted the expression of macrophage-derived cytokines to participate in liver fibrogenesis, and IL-1 alpha exhibited the most significant role in promoting the activation of HSCs and liver fibrogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available