xbp1s inhibitor  (MedChemExpress)

Journal: Cancer Research

Article Title: Nerves Stimulate Cross-talk Between Gastric Cancer and Group 3 Innate Lymphoid Cells to Enhance Immunosuppression

doi: 10.1158/0008-5472.CAN-25-3092

Figure Lengend Snippet: IL22 upregulates PD-L1 expression in gastric cancer cells through the UPR IRE1α–XBP1 axis. A, mIF images show the alterations of PD-L1 + tumor cells (purple), CD4 + (green), and CD8 + (red) T cells in orthotopic gastric cancer tumors from control and Abhd16a -knockdown mice following IL22 treatment. Scale bar, 50 μm. B, KEGG pathway enrichment analysis of RNA-seq data of gastric cancer tissues with or without IL22 treatment. C, RT-PCR was used to assess the mRNA expression of key downstream molecules of the UPR branches ( XBP1 , ATF4 , ATF6 ) in control and IL22RA1 -knockdown gastric cancer cells. D, Western blotting analysis of PD-L1 and XBP1s levels in control and IL22RA1 -knockdown MGC-803 cells treated with IL22 (100 μg/L). E, Western blotting detection of PD-L1 and XBP1s levels in XBP1- knockdown MGC-803 cells treated with IL22 and MGC-803 cells treated with IL22 or XBP1s inhibitor (STF083010, 30 μmol/L) in combination with IL22. F, The binding sequence of XBP1 on the CD274 promoter. G and H, ChIP ( G ) and luciferase reporter assay ( H ) showing the transcriptional regulation of CD274 by XBP1s under IL22 stimulation. I, Orthotopic gastric cancer mouse models ( n = 5 per group) were injected with anti-IL22 (200 μg per mouse), anti-CD90.2 antibody (150 μg per mouse), anti-CD90.2 antibody in combination with IL22 (500 ng per mouse), or anti-CD90.2 antibody in combination with XBP1s inhibitors (STF083010, 30 mg/kg) and IL22 for 2 weeks. IHC analysis was used to show IL22, XBP1s, and PD-L1 levels in gastric cancer tissues. Scale bar, 200 μm. J, Tumor volume of orthotopic gastric cancer models under treatments the same as in I . *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, nonsignificant.

Article Snippet: For the animal experiment, LysoPS (2.5 mg/kg, Sigma, 858144P), GPR34 inhibitor (GPR34 receptor antagonist 2, 20 mg/kg, MERYER, 907952), AKT inhibitor (perifosine, 20 mg/kg, MedChemExpress, HY-50909), XBP1s inhibitor (STF-083010, 30 mg/kg, MedChemExpress, HY-15845), IL22 Monoclonal Antibody (200 μg/mouse, eBioscience, 16-7222-82, RRID: AB_2016695), rmIL22 (500 ng/mouse, ABclonal, RP02942), and CD90.2 (150 μg/mouse, BioXCell, BE0066, RRID: AB_1107682) for ILC3 depletion were intraperitoneally injected once every 3 days.

Techniques: Expressing, Control, Knockdown, RNA Sequencing, Reverse Transcription Polymerase Chain Reaction, Western Blot, Binding Assay, Sequencing, Luciferase, Reporter Assay, Injection

Journal: Cancer Research

Article Title: Nerves Stimulate Cross-talk Between Gastric Cancer and Group 3 Innate Lymphoid Cells to Enhance Immunosuppression

doi: 10.1158/0008-5472.CAN-25-3092

Figure Lengend Snippet: Combination therapy enhances the anti–PD-L1 immunotherapeutic effect in gastric cancer. A and B, After tumor formation, the orthotopic gastric cancer mice ( n = 5 per group) were treated with anti–PD-L1 (100 μg per mouse), GPR34 inhibitor (20 mg/kg), or XBP1s inhibitor (30 mg/kg) every 3 days or ACh inhibitor (2.5 mg/kg) daily. Combinations of anti–PD-L1 with each inhibitor followed the every 3-day dosing schedule for a total duration of 2 weeks via i.p. injection. Living images were used to monitor tumor progression at 5-day intervals from the time of drug administration ( A ); IHC and mIF were performed to detect PD-L1 and XBP1s levels and proportions of CD4 + (green) and CD8 + (red) T cells in gastric cancer tissues at the end of treatments ( B ). Scale bars, 1.000e+5 –∼ 5.000e + 5 p/s/cm 2 /sr for living images; 200 μm for IHC; 50 μm for immunofluorescence. C and D, Representative images ( C ) and tumor volume ( D ) of subcutaneous tumors. The administration protocol for the mice was consistent with the description provided in A and B . **, P < 0.01; ***, P < 0.001.

Article Snippet: For the animal experiment, LysoPS (2.5 mg/kg, Sigma, 858144P), GPR34 inhibitor (GPR34 receptor antagonist 2, 20 mg/kg, MERYER, 907952), AKT inhibitor (perifosine, 20 mg/kg, MedChemExpress, HY-50909), XBP1s inhibitor (STF-083010, 30 mg/kg, MedChemExpress, HY-15845), IL22 Monoclonal Antibody (200 μg/mouse, eBioscience, 16-7222-82, RRID: AB_2016695), rmIL22 (500 ng/mouse, ABclonal, RP02942), and CD90.2 (150 μg/mouse, BioXCell, BE0066, RRID: AB_1107682) for ILC3 depletion were intraperitoneally injected once every 3 days.

Techniques: Injection, Immunofluorescence

Journal: Journal of hepatology

Article Title: Role of XBP1 in regulating the progression of non-alcoholic steatohepatitis.

doi: 10.1016/j.jhep.2022.02.031

Figure Lengend Snippet: Fig. 1. XBP1 is upregulated in the liver tissues of patients with NASH and macrophage Xbp1 depletion suppresses the development of experimental steatohepatitis. (A) The mRNA expression levels of XBP1 in liver tissues from patients with NASH (n = 46) and normal controls (n = 35). (B) The protein levels of XBP1 in the liver tissues of normal controls or patients with NASH were examined by western blot. (C) Representative H&E staining, Oil red O staining, and immunohistochemistry images of sXBP1 (400x) in the liver tissues from patients with NASH and normal controls; n = 6/group. (D) Dual immunofluorescence staining for CD68 and sXBP1 (400x) in liver tissues from patients with NASH and normal controls; n = 6/group. (E) Body weight in HFD-fed or chow-fed Xbp1DMf

Article Snippet: New Brunswick, CA) for 6 weeks (n = 6-8 per group).21 Wildtype C57BL/6 6-8-week-old male mice were administered intraperitoneal injections of the XBP1 inhibitor toyocamycin (0.5 Journal of Hepatology 2 mg/kg/day for consecutive 2 weeks),22 or the endoplasmic reticulum stress inhibitor tauroursodeoxycholic acid (TUDCA) (100 mg/kg/day for consecutive 2 weeks) (MedChemExpress, NJ, USA)23 or vehicle (Saline) after 24 weeks of HFD (n = 6-8 per group).

Techniques: Expressing, Western Blot, Staining, Immunohistochemistry

Journal: Journal of hepatology

Article Title: Role of XBP1 in regulating the progression of non-alcoholic steatohepatitis.

doi: 10.1016/j.jhep.2022.02.031

Figure Lengend Snippet: Fig. 2. Macrophage XBP1 induces M1 macrophage polarization and hepatocyte lipid accumulation. (A) Representative pictures of iNOS- and CD206-positive cells and the quantification in liver tissues from Xbp1DMf and Xbp1FL/FL mice fed with HFD; n = 6/group. (B) The protein levels of p-STAT1, STAT1, p-STAT6, and STAT6 in liver tissues from Xbp1DMf and Xbp1FL/FL mice fed with HFD. (C) Gene expression of Tnfa, Il6, Il1b, and Cxcl10 in liver tissues from Xbp1DMf and Xbp1FL/FL

Article Snippet: New Brunswick, CA) for 6 weeks (n = 6-8 per group).21 Wildtype C57BL/6 6-8-week-old male mice were administered intraperitoneal injections of the XBP1 inhibitor toyocamycin (0.5 Journal of Hepatology 2 mg/kg/day for consecutive 2 weeks),22 or the endoplasmic reticulum stress inhibitor tauroursodeoxycholic acid (TUDCA) (100 mg/kg/day for consecutive 2 weeks) (MedChemExpress, NJ, USA)23 or vehicle (Saline) after 24 weeks of HFD (n = 6-8 per group).

Techniques: Gene Expression

Journal: Journal of hepatology

Article Title: Role of XBP1 in regulating the progression of non-alcoholic steatohepatitis.

doi: 10.1016/j.jhep.2022.02.031

Figure Lengend Snippet: Fig. 3. Macrophage XBP1 promotes lipid accumulation and pro-inflammatory cytokines expression in hepatocytes by activating macrophage NLRP3 signaling pathway. (A) Schematic diagram showing that primary hepatocytes isolated from Xbp1FL/FL mice were co-cultured with LPS-primed primary bone marrow-derived or liver macrophages from Xbp1DMf and Xbp1FL/FL mice with or without PA. (B) Representative Oil Red O staining and TEM in primary hepatocytes co-cultured with primary bone marrow-derived macrophages after treatment with PA for 24 hours. (C) Representative Oil Red O staining and TEM in primary hepatocytes co-cultured with primary liver macrophages after treatment with PA for 24 hours. (D) The mRNA levels of Tnfa, Il6, and Il1b in palmitic acid-treated hepatocytes co-cultured with bone marrow-derived macrophages from Xbp1DMf and Xbp1FL/FL mice. (E) The mRNA levels of adipogenesis genes Pparg, Srebp-1c, ChREBP, and Fasn in hepatocytes co-cultured with bone marrow-derived macrophages from Xbp1DMf and Xbp1FL/FL mice in PA medium for 24 hours. (F) The mRNA levels of b-oxidation genes Ppara, Acadl, Acox, and Cpt1a in hepatocytes co-cultured with bone marrow-derived macrophages from Xbp1DMf and Xbp1FL/FL mice in PA medium. (G) Protein expression levels of NLRP3, C-caspase-1, pro-caspase-1, IL-1b, and pro-IL-1b in liver macrophages from Xbp1DMf and Xbp1FL/FL mice fed with HFD. (H) Protein expression levels of NLRP3, C-caspase-1, pro-caspase-1, IL-1b, and pro-IL-1b in LPS-primed bone marrow-derived macrophages treated with PA. (I) Representative H&E staining (400x), (J) NAS, (K) serum ALT levels and hepatic TG content in Nlrp3DMf and Nlrp3FL/FL mice fed the HFD; n = 6/group. (L) Representative pictures of Oil Red O-stained liver sections of Xbp1DMf and Xbp1FL/FL mice fed the HFD; n = 6/group. (M) Gene expression of Tnfa, Il6, Il1b, and Cxcl10 in liver tissues from Nlrp3DMf and Nlrp3FL/FL mice fed with HFD; n = 6/group. *p <0.05, **p <0.01 (unpaired t test or ANOVA). ALT, alanine aminotransferase; HFD, high-fat diet; LD, lipid droplets; LPS, lipopolysaccharide; NAS, NAFLD activity score; PA, palmitic acid; TEM, transmission electron microscopy; TG, triglyceride; XBP1, X-box binding protein-1.

Article Snippet: New Brunswick, CA) for 6 weeks (n = 6-8 per group).21 Wildtype C57BL/6 6-8-week-old male mice were administered intraperitoneal injections of the XBP1 inhibitor toyocamycin (0.5 Journal of Hepatology 2 mg/kg/day for consecutive 2 weeks),22 or the endoplasmic reticulum stress inhibitor tauroursodeoxycholic acid (TUDCA) (100 mg/kg/day for consecutive 2 weeks) (MedChemExpress, NJ, USA)23 or vehicle (Saline) after 24 weeks of HFD (n = 6-8 per group).

Techniques: Expressing, Isolation, Cell Culture, Derivative Assay, Staining, Gene Expression, Activity Assay, Transmission Assay, Electron Microscopy, Binding Assay

Journal: Journal of hepatology

Article Title: Role of XBP1 in regulating the progression of non-alcoholic steatohepatitis.

doi: 10.1016/j.jhep.2022.02.031

Figure Lengend Snippet: Fig. 4. Macrophage XBP1 induces lipid metabolism disorder and pro-inflammatory cytokine expression in hepatocytes via the activation of NLRP3 in vitro. (A) Schematic of primary hepatocytes from Nlrp3FL/FL mice co-cultured with LPS-primed primary bone marrow-derived macrophages from Nlrp3DMf mice or Nlrp3FL/FL mice with or without PA treatment. (B) Representative Oil Red O staining and TEM in primary Nlrp3FL/FL hepatocytes co-cultured with primary Nlrp3DMf or Nlrp3FL/FL bone marrow-derived macrophages after the addition of PA for 24 hours. (C) mRNA levels of Tnfa, Il6, and Il1b in PA-treated hepatocytes co- cultured with bone marrow-derived macrophages from Nlrp3DMf and Nlrp3FL/FL mice. (D) The mRNA levels of adipogenic genes Pparg, Srebp-1c, ChREBP, and Fasn

Article Snippet: New Brunswick, CA) for 6 weeks (n = 6-8 per group).21 Wildtype C57BL/6 6-8-week-old male mice were administered intraperitoneal injections of the XBP1 inhibitor toyocamycin (0.5 Journal of Hepatology 2 mg/kg/day for consecutive 2 weeks),22 or the endoplasmic reticulum stress inhibitor tauroursodeoxycholic acid (TUDCA) (100 mg/kg/day for consecutive 2 weeks) (MedChemExpress, NJ, USA)23 or vehicle (Saline) after 24 weeks of HFD (n = 6-8 per group).

Techniques: Expressing, Activation Assay, In Vitro, Cell Culture, Derivative Assay, Staining

Journal: Journal of hepatology

Article Title: Role of XBP1 in regulating the progression of non-alcoholic steatohepatitis.

doi: 10.1016/j.jhep.2022.02.031

Figure Lengend Snippet: Fig. 6. Macrophage Xbp1 depletion inhibits hepatic fibrosis and hepatic stellate cell activation by suppressing TGF-b1 expression. (A) The sections of liver tissues from Xbp1FL/FL and Xbp1DMf mice fed with HFD for 26 weeks or MCD diet for 6 weeks were subjected to Sirius red and a-SMA immunohistochemistry staining. n = 6 mice/group; original magnification ×400; scale bar = 50 lm. (B) The quantitative analysis of Sirius red and a-SMA immunohistochemistry staining in livers. n = 6 mice/group. (C) Primary hepatocyte-conditioned media was transferred to BMDMs primed with 10 ng/ml of LPS for 4 hours and then (D) BMDMs were subjected to RNA sequencing analysis after 48 hour incubation. n = 3/group. (E) The gene expression levels of Tgfb1 in LPS-primed Xbp1FL/FL and Xbp1DMf

Article Snippet: New Brunswick, CA) for 6 weeks (n = 6-8 per group).21 Wildtype C57BL/6 6-8-week-old male mice were administered intraperitoneal injections of the XBP1 inhibitor toyocamycin (0.5 Journal of Hepatology 2 mg/kg/day for consecutive 2 weeks),22 or the endoplasmic reticulum stress inhibitor tauroursodeoxycholic acid (TUDCA) (100 mg/kg/day for consecutive 2 weeks) (MedChemExpress, NJ, USA)23 or vehicle (Saline) after 24 weeks of HFD (n = 6-8 per group).

Techniques: Activation Assay, Expressing, Immunohistochemistry, Staining, RNA Sequencing, Incubation, Gene Expression

Journal: Journal of hepatology

Article Title: Role of XBP1 in regulating the progression of non-alcoholic steatohepatitis.

doi: 10.1016/j.jhep.2022.02.031

Figure Lengend Snippet: Fig. 7. Pharmacological inhibition of XBP1 prevents steatohepatitis in mice. (A) Schematic showing of HFD-fed WT mice treated with toyocamycin or TUDCA. (B) Liver weight in HFD-fed WT mice. (C) Representative H&E-staining, (D) NAS, (E) Oil Red O-stained liver sections, (F) serum ALT levels and (G) hepatic TG content in HFD-fed WT mice. (H) The hepatic mRNA expression levels of pro-inflammatory cytokines Tnfa, Il6, and Il1b in HFD-fed WT mice treated with or

Article Snippet: New Brunswick, CA) for 6 weeks (n = 6-8 per group).21 Wildtype C57BL/6 6-8-week-old male mice were administered intraperitoneal injections of the XBP1 inhibitor toyocamycin (0.5 Journal of Hepatology 2 mg/kg/day for consecutive 2 weeks),22 or the endoplasmic reticulum stress inhibitor tauroursodeoxycholic acid (TUDCA) (100 mg/kg/day for consecutive 2 weeks) (MedChemExpress, NJ, USA)23 or vehicle (Saline) after 24 weeks of HFD (n = 6-8 per group).

Techniques: Inhibition, Staining, Expressing