Journal: Scientific Reports

Article Title: IL-18 promotes pancreatic fibrosis via release of IL-4 from pancreatic stellate cells and induces macrophage M2 polarization

doi: 10.1038/s41598-026-38168-5

Figure Lengend Snippet: IL-18 expression in CP pancreatic tissues positively correlates with PF. (A) Immunofluorescence staining showed IL-18 expression and co-localization with acinar cells in human CP tissues compared to the normal pancreas ( n = 6). (B) IF for IL-18Rα in CP tissues ( n = 6). (C) Serum IL-18 concentrations in CP patients and controls measured by ELISA ( n = 8). (D) Histopathology (H&E) and fibrosis assessment by Masson’s trichrome ( n = 7). (E) IL-18 levels in pancreatic tissue homogenates from CP and normal samples ( n = 7–8). (F) Correlation analysis between tissue IL-18 expression and the fibrotic area in the same patient ( n = 7). ( G ) IL‑18 levels in PACs supernatants after CCK treatment. Data are mean ± SEM. ns, not significant, * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. Scale bar = 50 μm. Ctrl control, CP chronic pancreatitis. PACs pancreatic acinar cells. CCK Cholecystokinins.

Article Snippet: To validate the in vivo role of IL-18 mediated through IL-4, we administered 500 ng of recombinant mouse IL-18 (rmIL-18; #HY- P73181 , MedChemExpress) intraperitoneally three times a week, starting two weeks after the initial caerulein injection.

Techniques: Expressing, Immunofluorescence, Staining, Enzyme-linked Immunosorbent Assay, Histopathology, Control

Journal: Scientific Reports

Article Title: IL-18 promotes pancreatic fibrosis via release of IL-4 from pancreatic stellate cells and induces macrophage M2 polarization

doi: 10.1038/s41598-026-38168-5

Figure Lengend Snippet: IL-18 promotes IL-4 secretion by PSCs. (A , C) IF of human CP tissues showed IL-4 expression and co-localization with α-SMA ( n = 6). (B , D) Reduced pancreatic IL-4 expression in normal and chronic pancreatic tissues of both genotypes ( n = 3–5). (E) Schematic of primary murine PSC isolation and stimulation. (F) The purity of the extracted PSCs was evaluated by immunofluorescence detection of α-SMA. (G) PSCs were treated with rmIL-18, and qPCR was used to detect changes in the expression of IL-4, α-SMA, and TGF-β1 ( n = 5). (H) ELISA was used to measure changes in the IL-4 protein levels in the culture supernatant of PSCs treated with rmIL-18 ( n = 3). (I) Western blot results of PSCs after intervention Data are mean ± SEM. ns, not significant, * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. Scale bar = 30 μm. NS normal saline, Ctrl control, CP chronic pancreatitis. PSC pancreatic stellate cells.

Article Snippet: To validate the in vivo role of IL-18 mediated through IL-4, we administered 500 ng of recombinant mouse IL-18 (rmIL-18; #HY- P73181 , MedChemExpress) intraperitoneally three times a week, starting two weeks after the initial caerulein injection.

Techniques: Expressing, Isolation, Immunofluorescence, Enzyme-linked Immunosorbent Assay, Western Blot, Saline, Control

Journal: Scientific Reports

Article Title: IL-18 promotes pancreatic fibrosis via release of IL-4 from pancreatic stellate cells and induces macrophage M2 polarization

doi: 10.1038/s41598-026-38168-5

Figure Lengend Snippet: IL-18 drives M2 macrophage polarization via PSC-derived IL-4. (A) PSCs were cultured with or without rmIL-18, and then CM from different conditions were added to peritoneal macrophages seeded in plates. (B) The polarization of macrophages treated with CM, with or without the addition of IL-4 neutralizing antibody, was evaluated ( n = 3). (C , D) Western blot results of macrophages after intervention ( n = 3). (E , F) Quantitative PCR analysis of transcriptional levels of canonical M1 markers (iNOS, CD86) and M2 markers (CD206, YM-1) ( n = 3). Data are mean ± SEM. ns, not significant, * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. Scale bar = 30 μm. Ctrl control, Mac macrophage, CM conditioned media.

Article Snippet: To validate the in vivo role of IL-18 mediated through IL-4, we administered 500 ng of recombinant mouse IL-18 (rmIL-18; #HY- P73181 , MedChemExpress) intraperitoneally three times a week, starting two weeks after the initial caerulein injection.

Techniques: Derivative Assay, Cell Culture, Western Blot, Real-time Polymerase Chain Reaction, Control

Journal: Scientific Reports

Article Title: IL-18 promotes pancreatic fibrosis via release of IL-4 from pancreatic stellate cells and induces macrophage M2 polarization

doi: 10.1038/s41598-026-38168-5

Figure Lengend Snippet: IL-18 exacerbates CP severity in vivo via the IL-4/M2 axis. (A) WT mice with caerulein-induced CP received rmIL-18 with or without IL-4 neutralizing antibody. H&E and Masson’s trichrome staining images with fibrosis quantification; pancreatic IL-4 assessed by IF ( n = 3–5). Scale bar = 30 μm (B , C) IF analysis of macrophage polarization markers in macrophages treated with rmIL-18, with or without IL-4 inhibition. ( n = 3–5). Data are mean ± SEM. ns, not significant, * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. Scale bar = 50 μm. Ctrl control, CP chronic pancreatitis.

Article Snippet: To validate the in vivo role of IL-18 mediated through IL-4, we administered 500 ng of recombinant mouse IL-18 (rmIL-18; #HY- P73181 , MedChemExpress) intraperitoneally three times a week, starting two weeks after the initial caerulein injection.

Techniques: In Vivo, Staining, Inhibition, Control