SIRT2 deficiency modulates macrophage polarization and susceptibility to experimental colitis

Lo Sasso, Giuseppe; Menzies, Keir Joe; Mottis, Adrienne; Piersigilli, Alessandra; Perino, Alessia; Yamamoto, Hiroyasu; Schoonjans, Kristina; Auwerx, Johan (2014). SIRT2 deficiency modulates macrophage polarization and susceptibility to experimental colitis. PLoS ONE, 9(7), e103573. Public Library of Science 10.1371/journal.pone.0103573

[img]
Preview
Text
http___www.plosone.org_article_fetchObject.action_uri=info_doi_10.1371_journal.pone.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

BACKGROUND

SIRT2 belongs to a highly conserved family of NAD+-dependent deacylases, consisting of seven members (SIRT1-SIRT7), which vary in subcellular localizations and have substrates ranging from histones to transcription factors and enzymes. Recently SIRT2 was revealed to play an important role in inflammation, directly binding, deacetylating, and inhibiting the p65 subunit of NF-κB.

METHODS

A Sirt2 deficient mouse line (Sirt2-/-) was generated by deleting exons 5-7, encoding part of the SIRT2 deacetylase domain, by homologous recombination. Age- and sex-matched Sirt2-/- and Sirt2+/+ littermate mice were subjected to dextran sulfate sodium (DSS)-induced colitis and analyzed for colitis susceptibility.

RESULTS

Sirt2-/- mice displayed more severe clinical and histological manifestations after DSS colitis compared to wild type littermates. Notably, under basal condition, Sirt2 deficiency does not affect the basal phenotype and intestinal morphology Sirt2 deficiency, however, affects macrophage polarization, creating a pro-inflammatory milieu in the immune cells compartment.

CONCLUSION

These data confirm a protective role for SIRT2 against the development of inflammatory processes, pointing out a potential role for this sirtuin as a suppressor of colitis. In fact, SIRT2 deletion promotes inflammatory responses by increasing NF-κB acetylation and by reducing the M2-associated anti-inflammatory pathway. Finally, we speculate that the activation of SIRT2 may be a potential approach for the treatment of inflammatory bowel disease.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Piersigilli, Alessandra

Subjects:

600 Technology > 630 Agriculture

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Barbara Gautschi-Steffen

Date Deposited:

30 Mar 2015 15:00

Last Modified:

31 Mar 2015 20:16

Publisher DOI:

10.1371/journal.pone.0103573

PubMed ID:

25072851

BORIS DOI:

10.7892/boris.66386

URI:

https://boris.unibe.ch/id/eprint/66386

Actions (login required)

Edit item Edit item
Provide Feedback