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

被引：31

作者：

Keshari, Sunita ^{[1
]}

Sipayung, Apriska Dewi ^{[1
]}

Hsieh, Ching-Chuan ^{[3
]}

Su, Li-Jen ^{[2
]}

Chiang, Yun-Ru ^{[2
]}

Chang, Huan-Cheng ^{[4
]}

Yang, Wu-Chang ^{[4
]}

Chuang, Tsung-Hsien ^{[5
]}

Chen, Chien-Lung ^{[2
,4
]}

Huang, Chun-Ming ^{[1
,2
,6
]}

机构：

[1] Natl Cent Univ, Dept Life Sci, Taoyuan, Taiwan

[2] Natl Cent Univ, Dept Biomed Sci & Engn, Taoyuan, Taiwan

[3] Chang Gung Mem Hosp, Dept Surg, Div Gen Surg, Chiayi, Taiwan

[4] Landseed Hosp, Div Nephrol, Taoyuan, Taiwan

[5] Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan

[6] Univ Calif San Diego, Dept Dermatol, San Diego, CA 92103 USA

来源：

FASEB JOURNAL | 2019年 / 33卷 / 11期

关键词：

Bruton's tyrosine kinase; CaP; CKD; BRUTONS TYROSINE KINASE; POSITIVE FEEDBACK LOOP; CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR-DISEASE; MOUSE MODEL; HEMODIALYSIS-PATIENTS; SCRATCHING BEHAVIOR; BTK FUNCTION; ITCH; INTERLEUKIN-6;

D O I：

10.1096/fj.201900016RR

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：12036 / 12046

页数：11

共 59 条

[1] Nalfurafine Suppresses Pruritogen- and Touch-evoked Scratching Behavior in Models of Acute and Chronic Itch in Mice [J].