Journal Article

DKFZ-2026-02660

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png IL-18/IL-18R1 Involved in Pancreatic Fibrosis via Activating Pancreatic Stellate Cells

Aghamaliyev, U. ; Li, Z. ; Sirtl, S. ; Munker, S. ; Weniger, M. ; Yu, X. ; Lewis, A. ; Brohawn, P. Z. ; Astanova, B. ; Tan, K. ; Ceyhan, G. O. ; Bozkurt, M. ; Friess, H.DKFZ* ; Werner, J.DKFZ* ; Bazhin, A.DKFZ* ; D’Haese, J. G. ; Ilmer, M.DKFZ* ; Renz, B. W.DKFZ*

2026
Karger Basel

Abstract: Introduction: Chronic pancreatitis (CP) is a fibro-inflammatory syndrome characterized by irreversible tissue damage leading to exocrine and endocrine insufficiency, persistent pain, and an increased risk of pancreatic cancer. This study investigates the role of IL-18 in the activation process of pancreatic stellate cells (PSCs) and the progression of pancreatic fibrosis in CP. Methods: A total of 69 CP and 32 normal pancreatic tissue samples were analyzed using qRT-PCR and IHC to assess IL-18R1 expression. Primary PSCs were isolated from murine pancreata and cultured. Effects of recombinant IL-18 on PSC activation were evaluated using qRT-PCR and flow cytometry. Additionally, the impact of IL-18 binding protein (IL-18BP) and IL-18R1 antibody on PSC activation was examined. Results: IL-18R1 expression was significantly upregulated in CP tissues compared to normal pancreatic tissues, correlating with fibrosis severity. Cultured PSCs showed increased α-SMA and IL-18R1 expression over time, indicating activation. Treatment with recombinant IL-18 induced a dose-dependent increase in α-SMA expression, confirming PSC activation. Furthermore, cultured PSCs secreted IL-18, suggesting an autocrine activation mechanism. IL-18BP and IL-18R1 antibody treatments reduced PSC activation, underscoring IL-18’s regulatory role. Conclusion: Upregulation of IL-18R1 and its correlation with fibrosis severity in CP highlights the significant role of IL-18 in PSC activation and pancreatic fibrosis. These findings suggest that targeting the IL-18/IL-18R1 axis could be a promising therapeutic strategy to mitigate pancreatic fibrosis in CP, offering potential new avenues for treatment.

Note: #DKTKZFB9# / epub

---

Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

---

Database coverage:
; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF < 5 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---