d8 5 hete  (Cayman Chemical)

Journal: Cell Communication and Signaling : CCS

Article Title: Enterococcus faecalis -induced bystander effect causes epigenetic alterations leading to aberrant TGF-β signaling and epithelial-mesenchymal transition

doi: 10.1186/s12964-026-02735-0

Figure Lengend Snippet: E. faecalis activates Alox12 pathway in macrophages producing 12-HETE. A Targeted metabolomic analysis indicates significant alterations of arachidonic acid metabolites in the CM from E. faecalis -infected macrophages compared to CM from uninfected macrophages. Of these, a significant increase in 12-HETE is detected in the CM from both E. faecalis OG1RF- and WY84-infected macrophages compared to uninfected macrophages, while superoxide-deficient WY84 shows less efficiency (red arrow). B qRT-PCR reveals activation of Alox12 expression in macrophages treated with E. faecalis OG1RF and WY84. C and D Western blotting confirms elevated Alox12 in E. faecalis -infected macrophages. E qRT-PCR shows a significant increase in Alox12 expression in mouse bone marrow-derived macrophages (BMDMs) treated with E. faecalis OG1RF and WY84. F Western blots confirm increased Alox12 in E. faecalis -infected BMDMs. G ELISA shows a significant increase in the 12-HETE levels in CM from E. faecalis -infected BMDMs compared to that from uninfected BMDMs. H Western blots demonstrate significantly increased levels of H3K9ac and H3K27ac in IEC-6 cells treated with CM from E. faecalis -infected BMDMs compared to controls. I TCGA analysis shows a significant increase in ALOX12 expression in M1-polarized macrophages in human colon adenocarcinomas (COAD) and rectal adenocarcinomas (READ) compared to normal colon tissues. NS, not significant; * P < 0.05; ** P < 0.01; *** P < 0.001; and **** P < 0.0001 compared to controls. ## P < 0.01; ### P < 0.001 ; #### P < 0.0001 compared to OG1RF-infected macrophages

Article Snippet: 12-HETE and Alox12 inhibitor ML355 were purchased from MedChemExpress (Shanghai, China).

Techniques: Metabolomic, Infection, Quantitative RT-PCR, Activation Assay, Expressing, Western Blot, Derivative Assay, Enzyme-linked Immunosorbent Assay

Journal: Cell Communication and Signaling : CCS

Article Title: Enterococcus faecalis -induced bystander effect causes epigenetic alterations leading to aberrant TGF-β signaling and epithelial-mesenchymal transition

doi: 10.1186/s12964-026-02735-0

Figure Lengend Snippet: Inhibition of Alox12 decreases 12-HETE production by macrophages and reduces H3 acetylation in intestinal epithelial cells. A The quantitative RT-PCR assay for Alox12 gene expression indicates that ML355, an Alox12 inhibitor, unexpectedly enhances Alox12 gene transcription in RAW264.7 cells treated with E. faecalis OG1RF and WY84. B Western blots demonstrate a decrease in the protein levels of Alox12 in ML355-treated cells. C ELISA shows a significant decrease in the levels of 12-HETE in the CM from both uninfected and E. faecalis -infected RAW264.7 cells. D The levels of H3K9ac and H3K27ac are significantly decreased in IEC-6 cells following treatment with CM from both uninfected and E. faecalis -infected RAW264.7 cells exposed to ML355 compared to controls. ** P < 0.01; *** P < 0.001; and **** P < 0.0001 compared to controls. ### P < 0.001; #### P < 0.0001 compared to OG1RF-infected macrophages

Article Snippet: 12-HETE and Alox12 inhibitor ML355 were purchased from MedChemExpress (Shanghai, China).

Techniques: Inhibition, Quantitative RT-PCR, Gene Expression, Western Blot, Enzyme-linked Immunosorbent Assay, Infection

Journal: Cell Communication and Signaling : CCS

Article Title: Enterococcus faecalis -induced bystander effect causes epigenetic alterations leading to aberrant TGF-β signaling and epithelial-mesenchymal transition

doi: 10.1186/s12964-026-02735-0

Figure Lengend Snippet: 12-HETE mediates E. faecalis -induced BSE leading to H3 acetylation and TGF-β activation. A Representative Western blots for H3K27ac and H3K9ac in IEC-6 cells treated with 12-HETE at various doses. B 12-HETE enhances H3K27ac and H3K9ac levels after normalizing to β-actin. C Immunofluorescence staining confirms increased H3K27ac in IEC-6 cells treated with 12-HETE (500 nM) compared to untreated controls. D Representative photomicrographs of immunofluorescence staining for H3K27ac in murine colonic organoids. E The number of H3K27ac-positive cells significantly increased in colonic organoids treated with 12-HETE (500 nM) compared to untreated controls. F - H Western blotting reveals significantly decreased Id2 and increased levels of Fst and Nog in IEC-6 cells treated with 12-HETE compared to untreated controls after normalizing to β-actin. NS, not significant; * P < 0.05; ** P < 0.01; *** P < 0.001; and **** P < 0.0001 compared to controls

Article Snippet: 12-HETE and Alox12 inhibitor ML355 were purchased from MedChemExpress (Shanghai, China).

Techniques: Activation Assay, Western Blot, Immunofluorescence, Staining

Journal: Cell Communication and Signaling : CCS

Article Title: Enterococcus faecalis -induced bystander effect causes epigenetic alterations leading to aberrant TGF-β signaling and epithelial-mesenchymal transition

doi: 10.1186/s12964-026-02735-0

Figure Lengend Snippet: E. faecalis -induced BSE causes EMT. A Representative Western blots for E-cadherin and vimentin in IEC-6 cells. B and C Significantly reduced E-cadherin and increased vimentin are noted in cells treated with CM from E. faecalis -infected macrophages compared to controls after normalizing to β-actin. D - F Remarkably decreased E-cadherin and increased vimentin are noted in IEC-6 cells following repeatedly treated with 12-HETE for 10 cycles. G - I Immunofluorescent staining shows decreased Id2-positive cells in small intestinal biopsies from Il10 −/− mice colonized with E. faecalis OG1RF for both 10 and 90 days compared to mice colonized with WY84 or PBS sham. J - L E-cadherin expression is significantly decreased in intestinal biopsies from mice colonized with E. faecalis for both 10 and 90 days compared to controls. NS, not significant; * P < 0.05; ** P < 0.01; *** P < 0.001; and **** P < 0.0001 compared to controls

Article Snippet: 12-HETE and Alox12 inhibitor ML355 were purchased from MedChemExpress (Shanghai, China).

Techniques: Western Blot, Infection, Staining, Expressing

Journal: Cell Communication and Signaling : CCS

Article Title: Enterococcus faecalis -induced bystander effect causes epigenetic alterations leading to aberrant TGF-β signaling and epithelial-mesenchymal transition

doi: 10.1186/s12964-026-02735-0

Figure Lengend Snippet: Proposed mechanism for E. faecalis -induced histone H3 acetylation, TGF-β signaling, and EMT in intestinal epithelium. E. faecalis infection activates the Alox12 pathway in macrophages, leading to the production of 12-HETE, which induces pan-chromatin histone acetylation through a microbiota-induced bystander effect (MIBE). Alterations in histone H3 acetylation result in chromatin conformation changes and the activation of TGF-β signaling, ultimately promoting EMT and colorectal carcinogenesis

Article Snippet: 12-HETE and Alox12 inhibitor ML355 were purchased from MedChemExpress (Shanghai, China).

Techniques: Infection, Activation Assay

Journal: Redox Biology

Article Title: Neutrophil Irgm1 ameliorates sepsis-induced myocardial dysfunction by promoting Alox15 degradation

doi: 10.1016/j.redox.2026.104104

Figure Lengend Snippet: The regulatory role of Alox15/15-HETE in CLP-induced SIMD . (A) Graphs showing the levels of 15-HETE in the serum of WT and Irgm1-cKO mice after CLP (n = 5 per group). (B) Graphs showing the levels of 15-HETE in the supernatants of neutrophils from WT and Irgm1-cKO mice treated with LPS (n = 5 per group). (C) Schematic illustration of 15-HETE treatment in WT mice. The mice were intraperitoneally injected with 15-HETE (0.5 mg/kg). (D) Survival analysis of WT mice given Vehicle (n = 20) or 15-HETE (n = 26) after CLP was monitored for 24h. (E) Representative M-mode echocardiograms obtained from WT mice given Vehicle or 15-HETE after CLP. Scale bars = 2 mm (vertical) and 0.1 s (horizontal). (F–I) Echocardiographic measurements of left ventricular ejection fraction (EF, F), fractional shortening (FS, G), left ventricular internal diastolic dimension (LVIDD, H), and left ventricular end-diastolic volume (LVEDV, I) from WT mice given Vehicle or 15-HETE after CLP (n = 8 per group). (J) Relative ANP and BNP mRNA expression levels of the cardiac in WT mice given Vehicle or 15-HETE after CLP. (K and L) Graphs showing the levels of cTnI (K) and LDH (L) in the serum of WT mice given Vehicle or 15-HETE after CLP (n = 5 per group). (M) Relative mRNA expression levels of cardiac inflammation-related genes in WT mice given Vehicle or 15-HETE after CLP (n = 5 per group). (N) Representative images of H&E staining and quantitative analysis of myocardial injury. Scale bars: 50 μm for high magnification, 500 μm for low magnification. (O) TUNEL staining and quantification of apoptotic cardiomyocytes in heart tissues from WT mice given Vehicle or 15-HETE after CLP (n = 5 per group). Scale bar = 20 μm. (P) Representative TEM images of heart sections from WT mice given Vehicle or 15-HETE after CLP. Scale bars: 0.5 μm for high magnification, 1 μm for low magnification. Data are represented as the mean ± SD. Log-rank test for D. Unpaired Student t -test for A, and B, F through O. ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ∗∗∗∗ p < 0.0001.

Article Snippet: For pharmacological interventions, PD146176 (Alox15 inhibitor; 10 mg/kg, HY-103157, MedChemExpress) or 15-HETE (Arachidonic acid metabolites; 0.5 mg/kg, sc-200944, Santa Cruz Biotechnology) was administered intraperitoneally 15 min before CLP.

Techniques: Injection, Expressing, Staining, TUNEL Assay

Journal: Redox Biology

Article Title: Neutrophil Irgm1 ameliorates sepsis-induced myocardial dysfunction by promoting Alox15 degradation

doi: 10.1016/j.redox.2026.104104

Figure Lengend Snippet: Administration of PD146176 can eliminate the detrimental effects caused by Irgm1 deficiency in vivo . (A) Schematic illustration of PD146176 treatment in Irgm1-cKO mice. The mice were intraperitoneally injected with PD146176 (10 mg/kg). (B) Graphs showing the levels of 15-HETE in the serum of Irgm1-cKO mice given Vehicle or PD146176 after CLP (n = 5 per group). (C) Survival analysis of Irgm1-cKO mice given Vehicle (n = 24) or PD146176 (n = 18) after CLP performance was monitored for 24h. (D) Representative M-mode echocardiograms obtained from Irgm1-cKO mice given Vehicle or PD146176 after CLP. Scale bars = 2 mm (vertical) and 0.1 s (horizontal). (E-H) Echocardiographic measurements of left ventricular ejection fraction (EF, E), fractional shortening (FS, F), left ventricular internal diastolic dimension (LVIDD, G), and left ventricular end-diastolic volume (LVEDV, H) of Irgm1-cKO mice given Vehicle or PD146176 after CLP (n = 8 per group). Scale bars = 2 mm (vertical) and 0.1 s (horizontal). (I) Representative images of H&E staining and quantitative analysis of myocardial injury. Scale bars: 100 μm for high magnification, 500 μm for low magnification. (J and K) Graphs showing the levels of LDH (J) and cTnI (K) in the serum of Irgm1-cKO mice given Vehicle or PD146176 after CLP (n = 5 per group). (L) Relative ANP and BNP mRNA expression levels of the cardiac in Irgm1-cKO mice given Vehicle or PD146176 after CLP (n = 5 per group). (M) Relative mRNA expression levels of cardiac inflammation-related genes in Irgm1-cKO mice given Vehicle or PD146176 after CLP (n = 5 per group). (N) TUNEL staining and quantification of apoptotic cardiomyocytes in heart tissues from Irgm1-cKO mice given Vehicle or PD146176 after CLP (n = 5 per group). Scale bar = 20 μm. (O) Representative TEM images of heart sections from Irgm1-cKO mice given Vehicle or PD146176 after CLP. Scale bars: 0.5 μm for high magnification, 1 μm for low magnification. Data are represented as the mean ± SD. Log-rank test for C. Unpaired Student t -test for B, and E through N. ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ∗∗∗∗ p < 0.0001.

Article Snippet: For pharmacological interventions, PD146176 (Alox15 inhibitor; 10 mg/kg, HY-103157, MedChemExpress) or 15-HETE (Arachidonic acid metabolites; 0.5 mg/kg, sc-200944, Santa Cruz Biotechnology) was administered intraperitoneally 15 min before CLP.

Techniques: In Vivo, Injection, Staining, Expressing, TUNEL Assay

Journal: Cell Communication and Signaling : CCS

Article Title: Enterococcus faecalis -induced bystander effect causes epigenetic alterations leading to aberrant TGF-β signaling and epithelial-mesenchymal transition

doi: 10.1186/s12964-026-02735-0

Figure Lengend Snippet: E. faecalis activates Alox12 pathway in macrophages producing 12-HETE. A Targeted metabolomic analysis indicates significant alterations of arachidonic acid metabolites in the CM from E. faecalis -infected macrophages compared to CM from uninfected macrophages. Of these, a significant increase in 12-HETE is detected in the CM from both E. faecalis OG1RF- and WY84-infected macrophages compared to uninfected macrophages, while superoxide-deficient WY84 shows less efficiency (red arrow). B qRT-PCR reveals activation of Alox12 expression in macrophages treated with E. faecalis OG1RF and WY84. C and D Western blotting confirms elevated Alox12 in E. faecalis -infected macrophages. E qRT-PCR shows a significant increase in Alox12 expression in mouse bone marrow-derived macrophages (BMDMs) treated with E. faecalis OG1RF and WY84. F Western blots confirm increased Alox12 in E. faecalis -infected BMDMs. G ELISA shows a significant increase in the 12-HETE levels in CM from E. faecalis -infected BMDMs compared to that from uninfected BMDMs. H Western blots demonstrate significantly increased levels of H3K9ac and H3K27ac in IEC-6 cells treated with CM from E. faecalis -infected BMDMs compared to controls. I TCGA analysis shows a significant increase in ALOX12 expression in M1-polarized macrophages in human colon adenocarcinomas (COAD) and rectal adenocarcinomas (READ) compared to normal colon tissues. NS, not significant; * P < 0.05; ** P < 0.01; *** P < 0.001; and **** P < 0.0001 compared to controls. ## P < 0.01; ### P < 0.001 ; #### P < 0.0001 compared to OG1RF-infected macrophages

Article Snippet: 12-HETE and Alox12 inhibitor ML355 were purchased from MedChemExpress (Shanghai, China).

Techniques: Metabolomic, Infection, Quantitative RT-PCR, Activation Assay, Expressing, Western Blot, Derivative Assay, Enzyme-linked Immunosorbent Assay

Journal: Cell Communication and Signaling : CCS

Article Title: Enterococcus faecalis -induced bystander effect causes epigenetic alterations leading to aberrant TGF-β signaling and epithelial-mesenchymal transition

doi: 10.1186/s12964-026-02735-0

Figure Lengend Snippet: Inhibition of Alox12 decreases 12-HETE production by macrophages and reduces H3 acetylation in intestinal epithelial cells. A The quantitative RT-PCR assay for Alox12 gene expression indicates that ML355, an Alox12 inhibitor, unexpectedly enhances Alox12 gene transcription in RAW264.7 cells treated with E. faecalis OG1RF and WY84. B Western blots demonstrate a decrease in the protein levels of Alox12 in ML355-treated cells. C ELISA shows a significant decrease in the levels of 12-HETE in the CM from both uninfected and E. faecalis -infected RAW264.7 cells. D The levels of H3K9ac and H3K27ac are significantly decreased in IEC-6 cells following treatment with CM from both uninfected and E. faecalis -infected RAW264.7 cells exposed to ML355 compared to controls. ** P < 0.01; *** P < 0.001; and **** P < 0.0001 compared to controls. ### P < 0.001; #### P < 0.0001 compared to OG1RF-infected macrophages

Article Snippet: 12-HETE and Alox12 inhibitor ML355 were purchased from MedChemExpress (Shanghai, China).

Techniques: Inhibition, Quantitative RT-PCR, Gene Expression, Western Blot, Enzyme-linked Immunosorbent Assay, Infection

Journal: Cell Communication and Signaling : CCS

Article Title: Enterococcus faecalis -induced bystander effect causes epigenetic alterations leading to aberrant TGF-β signaling and epithelial-mesenchymal transition

doi: 10.1186/s12964-026-02735-0

Figure Lengend Snippet: Proposed mechanism for E. faecalis -induced histone H3 acetylation, TGF-β signaling, and EMT in intestinal epithelium. E. faecalis infection activates the Alox12 pathway in macrophages, leading to the production of 12-HETE, which induces pan-chromatin histone acetylation through a microbiota-induced bystander effect (MIBE). Alterations in histone H3 acetylation result in chromatin conformation changes and the activation of TGF-β signaling, ultimately promoting EMT and colorectal carcinogenesis

Article Snippet: 12-HETE and Alox12 inhibitor ML355 were purchased from MedChemExpress (Shanghai, China).

Techniques: Infection, Activation Assay