Biology subjects

Tour, J.

Publications and source records attributed to Tour, J..

4 recordsLinked to original sources

bioRxiv2022

Molecular machines stimulate intercellular calcium waves and cause muscle contraction

Intercellular calcium waves (ICW) are complex signaling phenomena that control many essential biological activities, including smooth muscle contraction, vesicle secretion, gene expression, and changes in neuronal excitability. Accordingly, the remote stimulation of ICW may result in versatile new biomodulation and therapeutic strategies. Here, we demonstrate that light-activated molecular machines (MM), molecules that rotate and perform mechanical work on the molecular scale, can remotely stimulate ICW. Live-cell calcium tracking and pharmacological experiments reveal that MM-induced ICW are driven by the activation of inositol triphosphate (IP3) mediated signaling pathways by unidirectional, fast-rotating MM. We then demonstrated that MM-induced ICW can be used to control muscle contraction in vitro in cardiomyocytes and animal behavior in vivo in Hydra vulgaris. Consequentially, this work demonstrates a new strategy for the direct control of cell signaling and downstream biological function using molecular-scale devices.

bioengineering↗

bioRxiv2022

Fibromyalgia patients with high levels of anti-satellite glia cell IgG antibodies present with more severe symptoms

ObjectiveTransferring fibromyalgia patient IgG to mice induces pain-like behaviour and fibromyalgia IgG binds mouse and human satellite glia cells (SGCs). These findings suggest that autoantibodies could be part of fibromyalgia pathology. However, it is unknown how frequently fibromyalgia patients have anti-SGC antibodies and how anti-SGC antibodies associate with disease severity. MethodsWe quantified serum or plasma anti-SGC IgG levels in two fibromyalgia cohorts from Sweden and Canada using an indirect immunofluorescence murine cell culture assay. Fibromyalgia serum IgG binding to human SGCs in human dorsal root ganglia tissue sections was assessed by immunofluorescence (n=14/group). ResultsIn the cell culture assay anti-SGC IgG levels were increased in both fibromyalgia cohorts compared to controls. Elevated anti-SGC IgG was associated with higher levels of self-reported pain in both cohorts, and higher fibromyalgia impact questionnaire scores and increased pressure sensitivity in the Swedish cohort. Anti-SGC IgG levels were not associated with fibromyalgia duration. Swedish FM patients were clustered into FM-severe and FM-mild groups and the FM-severe group had elevated anti-SGC IgG compared to the FM-mild and controls. Anti-SGC IgG levels detected in culture were positively correlated with increased binding to human SGCs. Moreover, the FM-severe group had elevated IgG binding to human SGCs compared to the FM-mild and control groups. ConclusionsA subset of fibromyalgia patients have elevated levels of anti-SGC antibodies, and the antibodies are associated with more severe fibromyalgia severity. Screening fibromyalgia patients for anti-SGC antibodies could provide a path to personalized treatment options that target autoantibodies and autoantibody production.

neuroscience↗

bioRxiv2019

Passive transfer of fibromyalgia pain from patients to mice.

Fibromyalgia syndrome (FMS) is a chronic pain condition characterized by widespread pain and tenderness1,2. The etiology and pathophysiology of fibromyalgia are unknown and there are no effective treatments. Here we show that sensory hypersensitivity in FMS is caused by autoantibodies that act by sensitizing nociceptive sensory neurons. Administration of IgG from FMS patients increased mouse pain sensitivities to stimulation with mechanical pressure and cold. In contrast, transfer of IgG depleted samples from FMS patients or IgG from healthy control subjects had no effect on pain sensitivity. Sensory nerve fibres in ex vivo skin-nerve preparations from mice treated with FMS IgG were hypersensitive to mechanical stimulation. Immunohistochemical analysis revealed that IgG from FMS patients specifically labeled satellite glial cells and myelinated fibre tracts, as well as a small number of macrophages and endothelial cells in mouse dorsal root ganglia but not skin, muscle, spinal cord and brain. Our results demonstrate that fibromyalgia pain is caused by IgG autoantibodies that sensitize peripheral nociceptive afferents neurons and suggest that therapies that reduce patient IgG titres may be effective treatments of fibromyalgia pain.

neuroscience↗

bioRxiv2018

Inducible Lung Epithelial Resistance Requires Multisource Reactive Oxygen Species Generation to Protect against Bacterial Infections

Pneumonia remains a global health threat, in part due to expanding categories of susceptible individuals and increasing prevalence of antibiotic resistant pathogens. However, therapeutic stimulation of the lungs mucosal defenses by inhaled exposure to a synergistic combination of Toll-like receptor (TLR) agonists known as Pam2-ODN promotes mouse survival of pneumonia caused by a wide array of pathogens. This inducible resistance to pneumonia relies on intact lung epithelial TLR signaling, and inducible protection against viral pathogens has recently been shown to require increased production of epithelial reactive oxygen species (ROS) from multiple epithelial ROS generators. To determine whether similar mechanisms contribute to inducible antibacterial responses, the current work investigates the role of ROS in therapeutically-stimulated protection against Pseudomonas aerugnosa challenges. Inhaled Pam2-ODN treatment one day before infection prevented hemorrhagic lung cytotoxicity and mouse death in a manner that correlated with reduction in bacterial burden. The bacterial killing effect of Pam2-ODN was recapitulated in isolated mouse and human lung epithelial cells, and the protection correlated with inducible epithelial generation of ROS. Scavenging or targeted blockade of ROS production from either dual oxidase or mitochondrial sources resulted in near complete loss of Pam2-ODN-induced bacterial killing, whereas deficiency of induced antimicrobial peptides had little effect. These findings support a central role for multisource epithelial ROS in inducible resistance against bacterial pathogens and provide mechanistic insights into means to protect vulnerable patients against lethal infections.

immunology↗