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A Signalling Cascade of IL-33 to IL-13 Regulates Metaplasia in the Mouse Stomach

A Signalling Cascade of IL-33 to IL-13 Regulates Metaplasia in the Mouse Stomach

Christine P Petersen, Anne R Meyer, Carlo De Salvo, Eunyoung Choi, Cameron Schlegel, Alec Petersen, Amy C Engevik, Nripesh Prasad, Shawn E Levy, R Stokes Peebles, Theresa T Pizarro, James R Goldenring

Gut. 2018 May;67(5):805-817.

PMID: 28196875

Abstract:

Objective:
Alternatively activated macrophages (M2) are associated with the progression of spasmolytic polypeptide-expressing metaplasia (SPEM) in the stomach. However, the precise mechanism(s) and critical mediators that induce SPEM are unknown.
Design:
To determine candidate genes important in these processes, macrophages from the stomach corpus of mice with SPEM (DMP-777-treated) or advanced SPEM (L635-treated) were isolated and RNA sequenced. Effects on metaplasia development after acute parietal cell loss induced by L635 were evaluated in interleukin (IL)-33, IL-33 receptor (ST2) and IL-13 knockout (KO) mice.
Results:
Profiling of metaplasia-associated macrophages in the stomach identified an M2a-polarised macrophage population. Expression of IL-33 was significantly upregulated in macrophages associated with advanced SPEM. L635 induced metaplasia in the stomachs of wild-type mice, but not in the stomachs of IL-33 and ST2 KO mice. While IL-5 and IL-9 were not required for metaplasia induction, IL-13 KO mice did not develop metaplasia in response to L635. Administration of IL-13 to ST2 KO mice re-established the induction of metaplasia following acute parietal cell loss.
Conclusions:
Metaplasia induction and macrophage polarisation after parietal cell loss is coordinated through a cytokine signalling network of IL-33 and IL-13, linking a combined response to injury by both intrinsic mucosal mechanisms and infiltrating M2 macrophages.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413395	IL-33 from mouse			Price

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