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Papers of the Week


Papers: 27 Jul 2019 - 2 Aug 2019


Animal Studies

PAIN TYPE:
Itch


2019 Nov


FASEB J


33


11

The IL-6/p-BTK/p-ERK signaling mediates the calcium phosphate-induced pruritus.

Authors

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
FASEB J. 2019 Nov; 33(11):12036-12046.
PMID: 31365830.

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. The IL-6/p-BTK/p-ERK signaling mediates the calcium phosphate-induced pruritus.