BACKGROUND: CD40 has been identified on a variety of cell types, and it plays an important role in adaptive immunity and inflammation. Peritoneal mesothelial cells (PMCs) are the main cell layer that line the peritoneal membrane. Previously we found that CD40 ligand (CD154) is functionally expressed on peritoneal macrophages during continuous ambulatory peritoneal dialysis peritonitis. However, there are few studies that have examined both CD40 expression on PMCs and the function of CD40 signalling in peritoneal local defence. The purpose of this study was to determine whether PMCs express CD40 and to investigate potential mechanisms of CD40-CD154 interactions that may be involved in the inflammation of the peritoneal membrane. METHODS: Rat PMCs were harvested from the peritoneal cavity and maintained under defined in vitro conditions. We examined expression of CD40 on PMCs under normal culture or stimulation with interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) or interleukin (IL)-1 by reverse transcription-polymerase chain reaction and fluorescence-activated cell sorting (FACS) analysis. After activation with CD40 monoclonal antibody (mAb), the expression of intercellular adhesion molecule-1 (ICAM-1) on PMCs was analysed by FACS. RESULTS: A portion of rat PMCs cultured in vitro expressed CD40 constitutively. The expression of CD40 mRNA and protein was upregulated markedly following stimulation with IFN-gamma, but not following IL-1 or TNF-alpha. The expression of ICAM-1 on PMCs was significantly increased after activation of CD40 with IFN-gamma and with CD40 mAb. CONCLUSION: PMCs functionally express CD40. The interaction between CD40 on PMCs and CD154-positive cells in the peritoneal cavity may play an important role in peritoneal local defence and may be involved in the inflammation process of the peritoneum.
BACKGROUND:CD40 has been identified on a variety of cell types, and it plays an important role in adaptive immunity and inflammation. Peritoneal mesothelial cells (PMCs) are the main cell layer that line the peritoneal membrane. Previously we found that CD40 ligand (CD154) is functionally expressed on peritoneal macrophages during continuous ambulatory peritoneal dialysis peritonitis. However, there are few studies that have examined both CD40 expression on PMCs and the function of CD40 signalling in peritoneal local defence. The purpose of this study was to determine whether PMCs express CD40 and to investigate potential mechanisms of CD40-CD154 interactions that may be involved in the inflammation of the peritoneal membrane. METHODS:Rat PMCs were harvested from the peritoneal cavity and maintained under defined in vitro conditions. We examined expression of CD40 on PMCs under normal culture or stimulation with interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) or interleukin (IL)-1 by reverse transcription-polymerase chain reaction and fluorescence-activated cell sorting (FACS) analysis. After activation with CD40 monoclonal antibody (mAb), the expression of intercellular adhesion molecule-1 (ICAM-1) on PMCs was analysed by FACS. RESULTS: A portion of rat PMCs cultured in vitro expressed CD40 constitutively. The expression of CD40 mRNA and protein was upregulated markedly following stimulation with IFN-gamma, but not following IL-1 or TNF-alpha. The expression of ICAM-1 on PMCs was significantly increased after activation of CD40 with IFN-gamma and with CD40 mAb. CONCLUSION: PMCs functionally express CD40. The interaction between CD40 on PMCs and CD154-positive cells in the peritoneal cavity may play an important role in peritoneal local defence and may be involved in the inflammation process of the peritoneum.
Authors: Joni M Prasad; Oscar Negrón; Xinli Du; Eric S Mullins; Joseph S Palumbo; Jessica M Gilbertie; Magnus Höök; Steven P Grover; Rafal Pawlinski; Nigel Mackman; Jay L Degen; Matthew J Flick Journal: Proc Natl Acad Sci U S A Date: 2020-12-21 Impact factor: 12.779