Basic—Liver, Pancreas, and Biliary TractLysophosphatidic Acid Is a Potential Mediator of Cholestatic Pruritus
Section snippets
Human Subjects
Peripheral venous blood was obtained from healthy donors, pregnant women, and patients with cholestatic disorders after informed consent according to the Declaration of Helsinki. The study was approved by the local medical ethical committees. Blood samples were immediately centrifuged at 4°C, and serum was frozen in aliquots at −80°C. ICP was diagnosed, as previously described,18 in pregnant women with pruritus who had no rash in conjunction with increased serum liver transaminase and/or bile
Neuron-Activating Serum Factor Identified as LPA
To identify potential pruritogens in cholestasis, we screened sera from pruritic patients for activation in different neuronal cell lines. We chose [Ca2+]i as an indicator of neuronal activation because it is a key mediator of the neuronal secretory response toward diverse receptor-dependent and -independent stimuli. In the human neuroblastoma cell line SH-SY5Y, we observed a dose-dependent increase in intracellular calcium concentrations with the addition of serum (Figure 1A). Interestingly,
Discussion
Pruritus is a common and disabling symptom in cholestatic liver diseases and many other systemic disorders, including renal insufficiency; endocrine, hematologic, and metabolic diseases; various infections; and certain malignancies. The causal factors of pruritus are unknown in most of these diseases. Here we provide clinical and experimental evidence that LPA is a potential mediator of cholestatic itch.
The discovery of itch-specific sensory neurons in the skin by Schmelz et al revolutionized
Acknowledgments
The authors thank Dr H. Reesink (Academic Medical Center, Amsterdam, The Netherlands) for kindly providing blood samples from patients with hepatitis C virus, Dr J. Aoki (University of Tokyo, Tokyo, Japan) for 5E5-autotaxin antibody, Dr H. van Lenthe (Academic Medical Center, Amsterdam, The Netherlands) for performing high-performance liquid chromatography/mass spectroscopy, and Jenny Chambers (Imperial College London, London, England) for her elaborate contribution to collection and
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by the Deutsche Forschungsgemeinschaft (KR3618/1-1 to A.E.K.).