L13a-dependent translational control in macrophages limits the pathogenesis of colitis

Darshana Poddar, Ravinder Kaur, William M. Baldwin, Barsanjit Mazumder

Research output: Contribution to journalArticlepeer-review

Abstract

Sustained inflammation from infiltrated immune cells plays a pivotal role in the pathogenesis of ulcerative colitis (UC). Previously, we established the role of ribosomal protein L13a in the regulation of an inflammation-responsive post-transcriptional operon in myeloid cells. However, the role of this protein as a molecular cue to control the severity of colitis is not known. Here, we examined whether L13a-dependent translational control in macrophages could serve as an endogenous defense against colitis. The administration of dextran sodium sulfate induced experimental colitis in myeloid-specific L13a-knockout (KO) and control mice. Pathological scoring and injury to the colon mucosa evaluated the severity of colitis. The steady-state levels of several pro-inflammatory cytokines and chemokines were determined through ELISA and polyribosome profile analysis. Rapid weight loss, severe rectal bleeding, shortening of the colon, and significantly reduced survival rate were observed in the KO mice. Histopathological analysis of the colons of KO mice showed a severe disruption of epithelial crypts with immune cell infiltrates. Elevated levels of several inflammatory cytokines and chemokines and abrogation of their naturally imposed translational silencing were observed in the colons of the KO mice. Higher serum levels of several pro-inflammatory cytokines and the release of gut bacteria and endotoxins into the blood streams of KO mice were detected, suggesting the amplification of the inflammatory response to septicemia. Taken together, these results reveal an essential role for L13a in the endogenous protection against UC and demonstrate the potential for new therapeutic opportunities through the deliberate promotion of this mechanism.

Original languageEnglish (US)
Pages (from-to)816-827
Number of pages12
JournalCellular and Molecular Immunology
Volume13
Issue number6
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Keywords

  • Inflammation
  • L13a, macrophages, translational control
  • Ulcerative colitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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