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Updated: Jul 11, 2026

A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
Published on: December 9, 2021
Protein kinase C-zeta (PKC-zeta) regulates Kupffer cell apoptosis during experimental sepsis
Yanhua Peng1, Celia A Sigua, Cynthia Karsonovich
1Department of Surgery, James A. Haley Veterans Affairs Medical Center, University of South Florida Health Sciences Center, C/O Tampa General Hospital, Tampa, FL 33601, USA.
Background:
Kupffer cells play an important role in sepsis-mediated liver injury. We tested the hypothesis that PKC-zeta plays a critical role in Kupffer cell apoptosis during sepsis.
Methods:
Sepsis was induced in rats by cecal ligation and puncture (CLP); 12 h later, livers were assayed for PKC-zeta, IKKalpha, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3, and DNA fragmentation. Kupffer cells from control rats were infected with AdPKC-zeta DN to inhibit PKC-zeta, or transfected with pCMVPKC-zeta to overexpress PKC-zeta, and then treated with lipopolysaccharide (LPS). Cellular extracts were assayed for PKC-zeta, IKKalpha, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3, and DNA fragmentation.
Results:
During sepsis, PKC-zeta localized in cells positive for the macrophage marker (F4/80). CLP upregulated PKC-zeta protein and activity, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3, and increased DNA fragmentation in rat livers (all p<0.001). AdPKC-zeta DN attenuated the LPS-induced upregulation of PKC-zeta activity, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3, and DNA fragmentation in Kupffer cells (all p<0.001), whereas overexpression of PKC-zeta augmented LPS-induced upregulation of IKKbeta, IKKgamma, NF-kappaB, Caspase-3, and DNA fragmentation (p<0.001).
Conclusion:
PKC-zeta plays an important role in sepsis-induced apoptosis of Kupffer cells via activation of NF-kappaB and Fas/FasL. Manipulating the response of Kupffer cells to cellular stress may have important therapeutic implications.
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