The Arginase and Rhodanese Activities of Certain Cell Strains after Long Cultivation <i>in Vitro </i>

Westfall, B. B.; Peppers, Ellison V.; Evans, Virginia J.; Sanford, Katherine K.; Hawkins, Naomi M.; Fioramonti, Mary C.; Kerr, Harold A.; Hobbs, Gwendolyn L.; Earle, Wilton R.

doi:10.1083/jcb.4.5.567

Cited by 16 publications

(1 citation statement)

References 22 publications

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“…The cytoplasmic Arg1 is efficiently induced by microbial compounds, hypoxia, and Th2 cytokines in myeloid, endothelial, and epithelial cells (12)(13)(14)(15). Constitutive expression of Arg1 is found in hepatocytes (16), innate lymphoid 2 cells (ILC2s) (17,18), and rat and human fibroblasts (19)(20)(21)(22). Numerous studies have reported an involvement of Arg1 in immune cell (dys)function.…”

Section: Introductionmentioning

confidence: 99%

Arginase impedes the resolution of colitis by altering the microbiome and metabolome

Baier

Gänsbauer

Giessler

et al. 2020

Journal of Clinical Investigation

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Arginase 1 (Arg1), which converts l-arginine into ornithine and urea, exerts pleiotropic immunoregulatory effects. However, the function of Arg1 in inflammatory bowel disease (IBD) remains poorly characterized. Here, we found that Arg1 expression correlated with the degree of inflammation in intestinal tissues from IBD patients. In mice, Arg1 was upregulated in an IL-4/ IL-13and intestinal microbiota-dependent manner. Tie2-Cre Arg1 fl/fl mice lacking Arg1 in hematopoietic and endothelial cells recovered faster from colitis than Arg1-expressing (Arg1 fl/fl) littermates. This correlated with decreased vessel density, compositional changes in intestinal microbiota, diminished infiltration by myeloid cells, and an accumulation of intraluminal polyamines that promote epithelial healing. The proresolving effect of Arg1 deletion was reduced by an l-arginine-free diet, but rescued by simultaneous deletion of other l-arginine-metabolizing enzymes, such as Arg2 or Nos2, demonstrating that protection from colitis requires l-arginine. Fecal microbiota transfers from Tie2-Cre Arg1 fl/fl mice into WT recipients ameliorated intestinal inflammation, while transfers from WT littermates into Arg1-deficient mice prevented an advanced recovery from colitis. Thus, an increased availability of l-arginine as well as altered intestinal microbiota and metabolic products accounts for the accelerated resolution from colitis in the absence of Arg1. Consequently, l-arginine metabolism may serve as a target for clinical intervention in IBD patients.

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