Nickel particles are present in Crohn's disease tissue and exacerbate intestinal inflammation in IBD susceptible mice

Hiroki Matsuda; Yoichi Nibe-Shirakihara; Akiko Tamura; Emi Aonuma; Satoko Arakawa; Kana Otsubo; Yasuhiro Nemoto; Takashi Nagaishi; Kiichiro Tsuchiya; Shigeomi Shimizu; Averil Ma; Mamoru Watanabe; Motohiro Uo; Ryuichi Okamoto; Shigeru Oshima

doi:10.1016/j.bbrc.2021.12.111

Nickel particles are present in Crohn's disease tissue and exacerbate intestinal inflammation in IBD susceptible mice

Biochem Biophys Res Commun. 2022 Feb 12:592:74-80. doi: 10.1016/j.bbrc.2021.12.111. Epub 2022 Jan 1.

Authors

Affiliations

¹ Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
² Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
³ Department of Advanced Therapeutics for G.I. Diseases, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
⁵ Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
⁶ Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
⁷ Department of Advanced Biomaterials, Tokyo Medical and Dental University, Tokyo, Japan.
⁸ Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: soshima.gast@tmd.ac.jp.

PMID: 35032835
DOI: 10.1016/j.bbrc.2021.12.111

Abstract

Crohn's disease is an inflammatory disease of the gut caused by a complex interplay among genetic, microbial, and environmental factors. The intestinal tract is constantly exposed to metals and other trace elements ingested as food. Synchrotron radiation-induced X-ray fluorescence spectroscopy and X-ray absorption fine structure analysis revealed the deposition of nickel particles within Crohn's disease tissue specimens. After nickel particle stimulation, THP-1 cells showed filopodia formation and autophagic vacuoles containing lipid bodies. Nickel particles precipitated colitis in mice bearing mutations of the IBD susceptibility protein A20/TNFAIP3. Nickel particles also exacerbated dextran sulfate sodium-induced colitis in mice harboring myeloid cell-specific Atg5 deficiency. These findings illustrate that nickel particle ingestion may worsen Crohn's disease by perturbing autophagic processes in the intestine, providing new insights into environmental factors in Crohn's disease pathogenesis.

Keywords: A20/TNFAIP3; Autophagy; Crohn's disease; Macrophage; Nickel.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy / drug effects
Autophagy-Related Protein 5 / metabolism
Crohn Disease / pathology*
Dextran Sulfate
Disease Progression*
Disease Susceptibility
Humans
Inflammation / pathology*
Intestines / pathology*
Macrophages / drug effects
Macrophages / pathology
Macrophages / ultrastructure
Mice
Mice, Inbred C57BL
Nickel / toxicity*
THP-1 Cells
Tumor Necrosis Factor alpha-Induced Protein 3 / metabolism

Substances

Autophagy-Related Protein 5
Nickel
Dextran Sulfate
Tumor Necrosis Factor alpha-Induced Protein 3