PGK1 modulates balance between pro- and anti-inflammatory cytokines by interacting with ITI-H4

• Published in: Biomedicine & pharmacotherapy Vol. 161; p. 114437
• Main Authors: Park, Hong-Beom, Choi, Bum-Chae, Baek, Kwang-Hyun
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.05.2023; Elsevier
• Subjects: Cytokines; Female; Humans; Inflammatory diseases; JAK2/STAT3 signaling pathway; Kinase; Mass spectrometry (MS); Phosphoglycerate Kinase - genetics; Pregnancy; Recurrent pregnancy loss (RPL); Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; NFAT5; DDX5; lncRNA; APS; ITI-H4; HIF-1α; Recurrent pregnancy loss (RPL); Inflammatory diseases; RPL; ISGs; RT-PCR; JAK2/STAT3 signaling pathway; PGK1; PP2A-Cβ; BKD; PGK2; PDHK1; MALDI-TOF/MS; PBS; VEGF; Mass spectrometry (MS); ICC; ILF2; PPARγ; DNAJC1; MASP-1; Kinase; IPTG; KLKB1; HSPA1B
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.114437

Inter-α-trypsin inhibitor heavy chain 4 (ITI-H4) is one of the acute phase proteins and is mainly related with inflammatory diseases such as bacterial bloodstream infection and recurrent pregnancy loss (RPL). In a previous study, ITI-H4 was reported to be cleaved by kallikrein B1 (KLKB1) and its cleaved form induces the imbalance between pro- and anti-inflammatory cytokines. Therefore, in this study, putative substrates of ITI-H4 were isolated by immunoprecipitation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analysis. Of those, phosphoglycerate kinase 1 (PGK1) was found to be a binding protein of ITI-H4. PGK1 increases the level of ITI-H4 expression and blocks the cleavage of ITI-H4 mediated by KLKB1. It also inhibits pro-inflammatory response by inhibiting the JAK2/STAT3 signaling pathway. Therefore, PGK1, a novel binding partner of ITI-H4, is expected to have cellular functions in the pathogenesis of ITI-H4-related inflammatory diseases. [Display omitted] •PGK1 is a novel binding partner of ITI-H4.•PGK1 increases the protein level of ITI-H4 and blocks the cleavage of ITI-H4 by KLKB1.•KLKB1 and PGK1 competitively bind to ITI-H4.•Threonine phosphorylation of ITI-H4 is regulated by PGK1.•PGK1 modulates pro- and anti-inflammatory response via the JAK2/STAT3 signaling pathway.