PMID- 34440067
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210830
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 9
IP  - 8
DP  - 2021 Jul 22
TI  - CD40 Agonist Monoclonal Antibody-Mediated Hepatitis in TNF-Receptor 1 Gene 
      Knockout Mice.
LID - 10.3390/biomedicines9080863 [doi]
LID - 863
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays an important role in liver 
      inflammation. CD40-CD40 ligand (CD40-CD40L) is a key receptor-ligand signaling 
      pair involved in the adaptive immune response and pathogenesis of autoimmune 
      diseases. In mice, CD40 activation leads to sickness behavior syndrome (SBS) 
      comprising weight loss, sleep disruption and depression, which can be blocked by 
      administration of the TNF-inhibitor etanercept. In the present study, we assessed 
      the extent of hepatic inflammation in mice devoid of the TNF-receptor 1 
      (TNFR1)-mediated signaling pathway. The TNFR1-depleted (TNFR1-/-) adult mice and 
      their wild type littermates were given a single intra-peritoneal injection of 
      CD40 agonist monoclonal antibody (mAb) or rat IgG2a isotope control. As described 
      previously, TNFR1-/- mice were protected from SBS upon CD40 mAb treatment. Cd40, 
      tnf and tnfr1 mRNA and Tnf-alpha peptide were increased in the liver of CD40 
      mAb-stimulated wild type mice. Serum alanine aminotransferase was elevated in 
      both CD40-activated wild type and TNFR1-/- mice. TNFR1-/- mice showed much less 
      intra-parenchymal infiltrates, hepatocellular necrosis, and perivascular clusters 
      upon CD40 mAb activation than their wild type littermates. A gene expression 
      microarray detected increased activity of metabolic and detoxification pathways 
      and decreased activity of inflammatory pathways. We conclude that immune 
      activation and development of liver inflammation in CD40L interactions depend on 
      TNFR1-mediated signaling pathways and are counteracted by alterations in 
      metabolic pathways.
FAU - Raabe, Oksana
AU  - Raabe O
AD  - Department of Biomedicine, University of Basel, 4056 Basel, Switzerland.
FAU - Birchler, Thomas
AU  - Birchler T
AD  - Institute of Experimental Immunology, University of Zurich, 8057 Zurich, 
      Switzerland.
FAU - Rehrauer, Hubert
AU  - Rehrauer H
AUID- ORCID: 0000-0001-7612-9394
AD  - Functional Genomics Center Zurich (FGCZ), ETH Zurich, University of Zurich, 8057 
      Zurich, Switzerland.
FAU - Eppler, Elisabeth
AU  - Eppler E
AD  - Institute of Anatomy, University of Zurich, 8057 Zurich, Switzerland.
AD  - Institute of Anatomy, University of Bern, 3012 Bern, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20210722
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC8389574
OTO - NOTNLM
OT  - CD40 activation
OT  - SBS
OT  - TNF receptor 1
OT  - TNF-alpha
OT  - autoimmune hepatitis
OT  - mouse model
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/28 06:00
MHDA- 2021/08/28 06:01
PMCR- 2021/07/22
CRDT- 2021/08/27 01:05
PHST- 2021/05/08 00:00 [received]
PHST- 2021/07/06 00:00 [revised]
PHST- 2021/07/14 00:00 [accepted]
PHST- 2021/08/27 01:05 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/08/28 06:01 [medline]
PHST- 2021/07/22 00:00 [pmc-release]
AID - biomedicines9080863 [pii]
AID - biomedicines-09-00863 [pii]
AID - 10.3390/biomedicines9080863 [doi]
PST - epublish
SO  - Biomedicines. 2021 Jul 22;9(8):863. doi: 10.3390/biomedicines9080863.