Loss of TLR3 and its downstream signaling accelerates acinar cell damage in the acute phase of pancreatitis.

  title={Loss of TLR3 and its downstream signaling accelerates acinar cell damage in the acute phase of pancreatitis.},
  author={Ivonne Regel and Susanne Raulefs and Simone Benitz and Charlotte Mihaljevic and Simon Rieder and Georg Leinenkugel and Katja Steiger and Anna Melissa Schlitter and Irene Esposito and Julia Mayerle and Bo Kong and J{\"o}rg Kleeff and Christoph W Michalski},
  journal={Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]},
  volume={19 1},
  • I. Regel, S. Raulefs, C. Michalski
  • Published 1 June 2016
  • Biology, Medicine
  • Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
Toll‐like receptor 3 expression in myeloid cells is essential for efficient regeneration after acute pancreatitis in mice
Evidence is provided that TLR3 signaling in myeloid cells is sufficient to limit inflammation and ADM formation and to promote regeneration after acute pancreatitis, and resolution of inflammation after AP was associated with macrophage sensitivity toTLR3‐mediated cell death.
Myeloid Differentiation Primary Response 88–Cyclin D1 Signaling in Breast Cancer Cells Regulates Toll-Like Receptor 3-Mediated Cell Proliferation
This study provides first comprehensive evidence on the involvement of canonical signaling of TLR3 using MyD88–cyclin D1-mediated breast cancer cell proliferation and will provide valuable insights into understanding theTLR3-mediated adjuvant therapy in cancer.


TLR9 and the NLRP3 inflammasome link acinar cell death with inflammation in acute pancreatitis.
BACKGROUND & AIMS Acute pancreatitis is characterized by early activation of intracellular proteases followed by acinar cell death and inflammation. Activation of damage-associated molecular pattern
TLR3 Can Directly Trigger Apoptosis in Human Cancer Cells1
It is shown that synthetic dsRNA induces apoptosis of human breast cancer cells in a TLR3-dependent manner, which involves the molecular adaptor Toll/IL-1R domain-containing adapter inducing IFN-β and type I IFN autocrine signaling, but occurs independently of the ds RNA-activated kinase.
dsRNA induces apoptosis through an atypical death complex associating TLR3 to caspase-8
Analysis of the caspase-8 activating machinery triggered in response to Poly(I:C) dsRNA uncovers a novel aspect of the molecular mechanisms involved during apoptosis induced by the innate immune receptor TLR3 in cancer cells.
Sterile inflammatory response in acute pancreatitis.
Genetic deletion and pharmacologic antagonism demonstrate that specific DAMP receptors, including Toll-like receptor (TLR) 4, TLR9, and P2X7, are also required for inflammation in experimental acute pancreatitis.
Possible involvement of Toll-like receptor 7 in the development of type 1 autoimmune pancreatitis
TLR7 might be key pattern-recognition receptors involved in the development of type 1 autoimmune pancreatitis, and this study investigated Toll-like receptors in type 1 AIP patients to clarify the pathogenesis.
Toll-like receptors as interferon-regulated genes and their role in disease.
  • J. Khoo, S. Forster, A. Mansell
  • Biology
    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
  • 2011
The function and role ofIFN-regulated TLRs in disease and how the role of IFN may impact upon TLR induction of the immune response in diseases are discussed, particularly in mouse models.
Activation of nuclear factor-κB in acinar cells increases the severity of pancreatitis in mice.
The level of NF-κB activation correlates with the severity of acute pancreatitis in mice and the findings indicate that strategies to inactivate NF-σB might be used to treat patients with acute or chronic pancreatitis.
Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3–mediated pathway
Mouse macrophages undergo receptor-interacting kinase-3 (RIP3)-dependent but TNF-α–independent necrosis when Toll-like receptors (TLR) 3 and 4 are activated by poly(I:C) and LPS, respectively, and these data indicate that there are multiple upstream necrosis-initiating signaling pathways converging on the RIP3 during an innate immune response to viral and bacterial infections in mammals.
TLR signaling by tumor and immune cells: a double-edged sword
The neoplastic process may usurp TLR signaling pathways to advance cancer progression, which suggests that targeting tumor TLR signaled pathways may open novel therapeutic avenues.