Study of the role of endoplasmic reticulum stress mediated apoptosis signal pathway in sepsis-induced splenic lymphocyte apoptosis

Abstract

To investigate the role of endoplasmic reticulum (ER) stress-mediated apoptosis signal pathway in extensive apoptosis of splenic lymphocytes in sepsis. Twenty-four C57BL/6 mice were randomized into the cecal ligation and puncture (CLP) group and sham operation group, with 12 mice in each group. Twenty-four hours after CLP, the animals were sacrificed, and spleens were harvested for evaluation. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis. The expressions of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. High degree of lymphocyte apoptosis was observed in the CLP group. Meanwhile, marked induction of GRP78 expression was observed in the splenocytes in septic mice, indicating the motivation of the unfolded protein responses (UPR). Furthermore, both mRNA and protein levels of CHOP were highly upregulated in the CLP group, suggesting that ER stress response was switched to a pro-apoptotic response. These results demonstrates activation of the ER stress response in lymphocytes and that ER stress may contribute to abnormal lymphocyte apoptosis during sepsis.