1. IL‐6/p‐BTK/p‐ERK signaling mediates calcium phosphate‐induced pruritus
- Author
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Tsung-Hsien Chuang, Chun Ming Huang, Wu Chang Yang, Sunita Keshari, Huan-Cheng Chang, Ching-Chuan Hsieh, Yun-Ru Chiang, Apriska Dewi Sipayung, Chien Lung Chen, and Li-Jen Su
- Subjects
Calcium Phosphates ,0301 basic medicine ,Uremic pruritus ,chemistry.chemical_element ,Calcium ,Pharmacology ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,Ganglia, Spinal ,Agammaglobulinaemia Tyrosine Kinase ,Genetics ,medicine ,Animals ,Bruton's tyrosine kinase ,Intradermal injection ,Phosphorylation ,Extracellular Signal-Regulated MAP Kinases ,Molecular Biology ,Skin ,Mice, Knockout ,biology ,Interleukin-6 ,Adenine ,Gene Expression Profiling ,Pruritus ,Research ,medicine.disease ,Mice, Inbred C57BL ,Pyrimidines ,030104 developmental biology ,chemistry ,Ibrutinib ,Knockout mouse ,biology.protein ,Pyrazoles ,Female ,Tyrosine kinase ,030217 neurology & neurosurgery ,Signal Transduction ,Biotechnology - Abstract
Uremic pruritus with elevated levels of calcium phosphate (CaP) in skin is a common symptom in patients with chronic kidney disease (CKD). In this study, we demonstrate that intradermal injection of CaP into mice triggered scratching by up-regulating the IL-6 in skin and phosphorylation of ERKs in dorsal root ganglion (DRG) in a dose-dependent manner. IL-6 is essential because the CaP-induced up-regulation of phosphorylated (p)-ERK in DRG was considerably reduced in the IL-6 knockout mice. Microarray analysis in conjunction with real-time PCR revealed a higher mRNA expression of Bruton’s tyrosine kinase (BTK) gene in DRG after CaP injection. The inhibition of BTK by ibrutinib noticeably diminish the CaP-induced up-regulation of IL-6 and p-ERK in mice. A high amount of IL-6 was detected in itchy skin and blood of patients with CKD. The expressions of p-BTK and p-ERK in DRG primary cells reached maximum levels at 1 and 10 min, respectively, after treatment of recombinant IL-6 and were significantly reduced by treatment of IL-6 along with ibrutinib. The mechanism by which the CaP-induced pruritus mediated by the IL-6/p-BTK/p-ERK signaling was revealed.—Keshari, S., Sipayung, A. D., Hsieh, C.-C., Su, L.-J., Chiang, Y.-R., Chang, H.-C., Yang, W.-C., Chuang, T.-H., Chen, C.-L., Huang, C.-M. IL-6/p-BTK/p-ERK signaling mediates calcium phosphate–induced pruritus.
- Published
- 2019