Reduction of Chemokine CXCL9 Expression by Omega-3 Fatty Acids via ADP-Ribosylhydrolase ARH3 in MIN6 Insulin-Producing Cells

You, Youngki; Sarkar, Soumyadeep; Deiter, Cailin; Elliott, Emily C.; Nicora, Carrie D.; Mirmira, Raghavendra G.; Sussel, Lori; Nakayasu, Ernesto S.

doi:10.1002/pmic.202400053

Title: Reduction of Chemokine CXCL9 Expression by Omega-3 Fatty Acids via ADP-Ribosylhydrolase ARH3 in MIN6 Insulin-Producing Cells

Journal Article · 08 December 2024 · Proteomics

DOI: https://doi.org/10.1002/pmic.202400053 · OSTI ID:2527348

You, Youngki ^[1]; Sarkar, Soumyadeep ^[1]; Deiter, Cailin ^[2]; Elliott, Emily C. ^[1];

^[1]; Mirmira, Raghavendra G. ^[3]; Sussel, Lori ^[2];

^[1]

Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Univ. of Colorado, Aurora, CO (United States). Anschutz Medical Center
Univ. of Chicago, IL (United States)

Type 1 diabetes (T1D) results from the autoimmune destruction of the insulin-producing β cells of the pancreas. Omega-3 fatty acids protect β cells and reduce the incidence of T1D, but the mechanism is poorly understood. We have shown that omega-3 fatty acids reduce pro-inflammatory cytokine-mediated β-cell apoptosis by upregulating the expression of the ADP-ribosylhydrolase ARH3. Here, we further investigate the β-cell protection mechanism of ARH3 by performing siRNA analysis of its gene Adprhl2 in MIN6 insulin-producing cells, subsequent treatment with a cocktail of the pro-inflammatory cytokines IL-1β + IFN-γ + TNF-α, followed by proteomics analysis. ARH3 regulated proteins from several pathways related to the nucleus (splicing, RNA surveillance, and nucleocytoplasmic transport), mitochondria (metabolic pathways), and endoplasmic reticulum (protein folding). ARH3 also regulated the levels of proteins related to antigen processing and presentation, and the chemokine-signaling pathway. We further studied the role of ARH3 in regulating the chemokine CXCL9. We found that ARH3 reduces the cytokine-induced expression of CXCL9, which is dependent on omega-3 fatty acids. In conclusion, we demonstrate that omega-3 fatty acids regulate CXCL9 expression via ARH3, which may have a role in protecting β cells from immune attack thereby preventing T1D development.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2527348

Report Number(s):: PNNL-SA--206213

Journal Information:: Proteomics, Journal Name: Proteomics Journal Issue: 3 Vol. 25; ISSN 1615-9853

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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Title: Reduction of Chemokine CXCL9 Expression by Omega-3 Fatty Acids via ADP-Ribosylhydrolase ARH3 in MIN6 Insulin-Producing Cells

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