Fatostatin ameliorates inflammation without affecting cell viability. Issue 3 (1st February 2022)

• Record Type: Journal Article
• Authors: Ma, Shuhe; Murakami, Kosaku; Tanaka, Kazune; Hashimoto, Motomu; Tanaka, Masao; Kitagori, Koji; Akizuki, Shuji; Nakashima, Ran; Yoshifuji, Hajime; Ohmura, Koichiro; Morinobu, Akio; Mimori, Tsuneyo
• Is Part Of: FEBS open bio. Volume 12:Issue 3(2022)
• Page Start: 594
• Page End: 604
• Publication Date: 2022-02-01
• Subjects: cytokine -- fatostatin -- inflammation -- lipid -- SREBP; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.13364
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : The mature form of sterol regulatory element‐binding protein (SREBP)1 is a transcription factor involved in lipid synthesis, which participates in toll like receptor 4‐triggered inflammatory pathways during the resolution phase of inflammation in macrophages. SREBP1 has thus attracted interest as a candidate target molecule for ameliorating inflammation. Fatostatin is a small molecule that inhibits the maturation and function of SREBP, and its role in regulating inflammation is poorly understood. To evaluate the anti‐inflammatory effect of fatostatin, we compared body weight, footpad and hock dimensions, and arthritis scores between K/BxN serum‐induced arthritis mice treated with fatostatin and those treated with dimethyl sulfoxide as the vehicle control. We performed hematoxylin and eosin staining of joints of distal paws to assess tissue inflammation. Moreover, inflammatory cytokine production levels and cell viability were measured in lipopolysaccharide‐responsive human embryonic kidney 293 cells (293/hTLR4A‐MD2‐CD14 cells) after fatostatin administration. In K/BxN serum‐induced arthritis mice, fatostatin treatment significantly reduced the arthritis scores and hyperplasia. In vitro analysis revealed that fatostatin significantly inhibited the secretion of inflammatory cytokines from cells activated with lipopolysaccharide, without affecting cell viability. This is the first study to demonstrate that fatostatin is an anti‐inflammatory agent that modulates the processing of lipid transcription factors without affecting cell viability. Accordingly, the study reveals the potential of anti‐inflammatory therapeutics that link lipid regulation and inflammation. Abstract : Fatostatin is a small molecule that inhibits the function of sterol regulatory element‐binding protein 1. In the present study, we found that fatostatin acts as an anti‐inflammatory agent without affecting cell viability. In K/BxN serum‐induced arthritis mice, fatostatin treatment significantly reduced arthritis scores and hyperplasia. In vitro analysis revealed that fatostatin significantly inhibits the secretion of inflammatory cytokines from cells activated with lipopolysaccharide, without affecting cell viability.