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Pharmacological Targeting of the ER-Resident Chaperones GRP94 or Cyclophilin B Induces Secretion of IL-22 Binding Protein Isoform-1 (IL-22BPi1).

Int J Mol Sci. 2019; 
Gómez-FernándezPaloma,UrtasunAndoni,AstobizaIanire,MenaJorge,AllozaIraide,Vandenbroeck
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Molecular Biology Reagents IL22RA2i2 and IL22RA2i3 expression plasmids were purchased from OriGene (RC219095, Rockville, MD, USA) and GenScript (Ohu00490, Piscataway, NJ, USA), respectively.... For immunoblotting, the antibodies used in this study are the following: anti-FLAG (1:1000, 2043-1-AP, Proteintech, Rosemont, IL, USA); anti-IL-22BP (1:1000, AF1087, R&D Systems, Minneapolis, MN, USA); anti-GRP94 (1:1000, ADI-SPA-850, Enzo, Farmingdale, NY, USA); anti-pAkt (1:500, 9271, Cell signaling, Danvers, MA, USA); anti-PPIB (1:5000, 16045, Abcam, Cambridge, UK); anti-actin (1:1000, A2066, Sigma); anti-PPIC (1:1000, 10287-2-AP, Proteintech); anti-tubulin (1:1000, A01490, GenScript); and all HRP-conjugated secondary antibodies were purchased from Jackson ImmunoResearch. Get A Quote

摘要

Of the three interleukin-22 binding protein (IL-22BP) isoforms produced by the human gene, IL-22BPi2 and IL-22BPi3 are capable of neutralizing IL-22. The longest isoform, IL-22BPi1, does not bind IL-22, is poorly secreted, and its retention within the endoplasmic reticulum (ER) is associated with induction of an unfolded protein response (UPR). Therapeutic modulation of IL-22BPi2 and IL-22BPi3 production may be beneficial in IL-22-dependent disorders. Recently, we identified the ER chaperones GRP94 and cyclophilin B in the interactomes of both IL-22BPi1 and IL-22BPi2. In this study, we investigated whether secretion of the IL-22BP isoforms could be modulated by pharmacological targeting of GRP94 ... More

关键词

BiP,ER,GRP78,GRP94,IL-22BP,IL22RA2,UPR,cyclophilin,cyclosporin A,geldanamycin,gp96,iso