Blockade of CCR5 suppresses paclitaxel-induced peripheral neuropathic pain caused by increased deoxycholic acid.

Autor:	Zhong S; Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China; Liaoning Provincial Key Laboratory of Big Data for Neurological Diseases, Shenyang, Liaoning 110001, China., Liu F; Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China., Giniatullin R; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland., Jolkkonen J; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland., Li Y; Department of Biochemistry and Molecular Cell Biology, Institution of Medicine Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Zhou Z; Department of Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China., Lin X; Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China., Liu C; Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China; Liaoning Provincial Key Laboratory of Big Data for Neurological Diseases, Shenyang, Liaoning 110001, China., Zhang X; Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China; Liaoning Provincial Key Laboratory of Big Data for Neurological Diseases, Shenyang, Liaoning 110001, China., Liu Z; Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China., Lv C; Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China., Guo Q; Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China., Zhao C; Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China; Liaoning Provincial Key Laboratory of Big Data for Neurological Diseases, Shenyang, Liaoning 110001, China. Electronic address: cszhao@cmu.edu.cn.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Nov 28; Vol. 42 (11), pp. 113386. Date of Electronic Publication: 2023 Nov 09.
DOI:	10.1016/j.celrep.2023.113386
Abstrakt:	Paclitaxel leads to peripheral neuropathy (paclitaxel-induced peripheral neuropathy [PIPN]) in approximately 50% of cancer patients. At present, there are no effective treatment strategies for PIPN, the mechanisms of which also remain unclear. In this study, we performed microbiome and metabolome analysis of feces and serum from breast cancer patients with different PIPN grades due to paclitaxel treatment. Our analysis reveals that levels of deoxycholic acid (DCA) are highly increased because of ingrowth of Clostridium species, which is associated with severe neuropathy. DCA, in turn, elevates serum level of C-C motif ligand 5 (CCL5) and induces CCL5 receptor 5 (CCR5) overexpression in dorsal root ganglion (DRG) through the bile acid receptor Takeda G-protein-coupled receptor 5 (TGR5), contributing to neuronal hyperexcitability. Consistent with this, administration of CCR5 antagonist maraviroc suppresses the development of neuropathic nociception. These results implicate gut microbiota/bile acids/CCR5 signaling in the induction of PIPN, thus suggesting a target for PIPN treatment. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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