Journal article

Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation

H Kitamura, S Kimura, Y Shimamoto, J Okabe, M Ito, T Miyamoto, Y Naoe, C Kikuguchi, B Meek, C Toda, S Okamoto, K Kanehira, K Hase, H Watarai, M Ishizuka, A El-Osta, O Ohara, I Miyoshi

FASEB Journal | FEDERATION AMER SOC EXP BIOL | Published : 2013

Abstract

Macrophages play a critical role in chronic inflammation and metabolic diseases. We identified a longer splice variant of ubiquitin specific protease (USP) 2-69 as a novel molecule that modulates pathways implicated in metabolic disorders. Expression levels of aP2/ FABP4 and PAI-1/SERPINE1 genes were increased by 4- and 1.8-fold, respectively, after short hairpin RNA-mediated knockdown (KD) of the USP2 gene, and such expression was alleviated by overexpression of USP2-69 in human myeloid cell lines. Supernatants derived from USP2-KD cells induced IL6 (6-fold) and SAA3 (15-fold) in 3T3-L1 adipocytes to suggest the anti-inflammatory properties of USP2. In addition, we observed a 30% decrease i..

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University of Melbourne Researchers

Grants

Awarded by Japan Society for the Promotion of Science


Funding Acknowledgements

The authors thank Atsuo Kobayashi, Tomoko Yuasa, Tomoko Hasegawa, Saori Hayashi, Ryosuke Yashi, Dr. Mai Yamagishi, and Dr. Fumihiko Ishikawa at RIKEN, Prof. Toshihiko Iwanaga at Hokkaido University, and Satoshi Tanaka at Nippon Becton Dickinson Company for technical assistance. This study was supported by the Japan Society for the Promotion of Science Kakenhi (21790334 and 80312403), Takeda Science Foundation, Ono Medical Research Foundation, Mochida Memorial Foundation, Suzuken Memorial Foundation, Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care, Novartis Foundation, Nitto Foundation, and AstraZeneca.