Activin A signaling stimulates neutrophil activation and macrophage migration in pancreatitis.

Autor: Wiley MB; Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA., Bauer J; Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA., Alvarez V; Department of Biochemistry, University of Washington, Seattle, WA, 98195, USA., Mehrotra K; Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA., Cheng W; Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA., Kolics Z; Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA., Giarrizzo M; Department of Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794, USA., Ingle K; Department of Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794, USA., Bialkowska AB; Department of Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794, USA., Jung B; Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA. bhjung@uw.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Apr 23; Vol. 14 (1), pp. 9382. Date of Electronic Publication: 2024 Apr 23.
DOI: 10.1038/s41598-024-60065-y
Abstrakt: Acute Pancreatitis (AP) is associated with high mortality and current treatment options are limited to supportive care. We found that blockade of activin A (activin) in mice improves outcomes in two murine models of AP. To test the hypothesis that activin is produced early in response to pancreatitis and is maintained throughout disease progression to stimulate immune cells, we first performed digital spatial profiling (DSP) of human chronic pancreatitis (CP) patient tissue. Then, transwell migration assays using RAW264.7 mouse macrophages and qPCR analysis of "neutrophil-like" HL-60 cells were used for functional correlation. Immunofluorescence and western blots on cerulein-induced pancreatitis samples from pancreatic acinar cell-specific Kras knock-in (Ptf1aCre ER ™; LSL-Kras G12D ) and functional WT Ptf1aCre ER ™ mouse lines mimicking AP and CP to allow for in vivo confirmation. Our data suggest activin promotes neutrophil and macrophage activation both in situ and in vitro, while pancreatic activin production is increased as early as 1 h in response to pancreatitis and is maintained throughout CP in vivo. Taken together, activin is produced early in response to pancreatitis and is maintained throughout disease progression to promote neutrophil and macrophage activation.
(© 2024. The Author(s).)
Databáze: MEDLINE
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