Publications by authors named "Ralph G Tieland"

Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts of extracellular matrix components such as collagen interferes with organ function. LAIR-1 is an inhibitory collagen receptor highly expressed on tissue immune cells. We questioned whether in SSc, impaired LAIR-1-collagen interaction is contributing to the ongoing inflammation and fibrosis.

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Neutrophils are crucial innate immune cells but also play key roles in various diseases, such as cancer, where they can perform both pro- and anti-tumorigenic functions. To study the function of neutrophils in vivo, these cells are often depleted using Ly-6G or Gr-1 depleting antibodies or genetic "knockout" models. However, these methods have several limitations, being only partially effective, effective for a short term, and lacking specificity or the ability to conditionally deplete neutrophils.

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Fibrosis is a major cause of mortality worldwide, characterized by myofibroblast activation and excessive extracellular matrix deposition. Systemic sclerosis is a prototypic fibrotic disease in which CXCL4 is increased and strongly correlates with skin and lung fibrosis. Here we aim to elucidate the role of CXCL4 in fibrosis development.

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Objective: SSc is a complex disease characterized by vascular abnormalities and inflammation culminating in hypoxia and excessive fibrosis. Previously, we identified chemokine (C-X-C motif) ligand 4 (CXCL4) as a novel predictive biomarker in SSc. Although CXCL4 is well-studied, the mechanisms driving its production are unclear.

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Article Synopsis
  • The study investigates the role of plasmacytoid dendritic cells (pDCs) in systemic sclerosis (SSc), an autoimmune disease characterized by inflammation and fibrosis, focusing on pathways affecting pDC function.
  • Researchers analyzed pDCs from over 1,190 SSc patients and found that lower levels of the transcription factor RUNX3, linked to gene methylation and hypoxia, may contribute to SSc susceptibility.
  • The results indicate that loss of RUNX3 in pDCs leads to increased skin fibrosis in mouse models, highlighting pDCs' significant role in the disease's progression and potential therapeutic targets.
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Introduction: The methoxamine-sensitized rabbit model is widely used to screen drugs for proarrhythmic properties, especially repolarization-dependent TdP arrhythmias. With the change of anesthesia and/or sensitizing agent, conduction disturbances have been reported as well. Therefore, we compared currently available in-house anesthetics in order to preserve arrhythmia sensitivity and preclude conduction disturbances.

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The anesthetized chronic AV-blocked dog (cAVB) and methoxamine-sensitized rabbit model are widely used to determine pro-arrhythmic properties of drugs. In general, both models show similar results. However, conflicting data have also been reported; K201 and AZD1305 induced Torsade de Pointes (TdP) exclusively in cAVB dogs.

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Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. We showed that the antiprotozoic pentamidine decreased K(IR)2.x carried I(K1) current and that inhibiting protein degradation in the lysosome increased intracellular K(IR)2.

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