PTPRO exaggerates inflammation in ulcerative colitis through TLR4/NF-κB pathway

J Cell Biochem. 2020 Feb;121(2):1061-1071. doi: 10.1002/jcb.29343. Epub 2019 Aug 26.

Abstract

Previous studies have implicated protein tyrosine phosphatase receptor type O (PTPRO) as a key regulator in inflammation-associated diseases; however, its role in ulcerative colitis (UC) remains largely unknown. Thus, we aim to elucidate the potential role and underlying mechanism of PTPRO in UC. In this study, increased expression of PTPRO, toll-like receptor (TLR4) and inflammatory cytokines were observed in mucosal tissues (MTs) from inflamed areas and lamina propria mononuclear cells (LPMCs) of patients with UC compared with those from healthy controls. Then, it was manifested that PTPRO promoted the expression of TLR4 and proinflammatory cytokines in lipopolysaccharide-induced (LPS-induced) inflammatory macrophage model. Besides, PTPRO inhibited the proliferation of intestinal epithelial cells (IECs) but enhanced the apoptosis of IECs in macrophages. Moreover, levels of phosphorylated nuclear factor κB (NF-κB)/p65 and inhibitor of NF-κB α (IκBα) were more significantly increased in PTPRO overexpressed macrophages. In addition, the area under receiver operating characteristic curve was 0.807 (95%CI = 0.686-0.958, P < .001) suggesting PTPRO as an ideal diagnostic marker for UC. Taken these, the present study shows strong evidence that PTPRO exaggerates inflammation in UC via TLR4/NF-κB signaling pathway.

Keywords: nuclear factor κB; protein tyrosine phosphatase receptor type O; toll-like receptor 4; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Case-Control Studies
  • Colitis, Ulcerative / complications*
  • Cytokines / metabolism
  • Humans
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Macrophages / metabolism
  • Macrophages / pathology*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / metabolism*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Cytokines
  • NF-kappa B
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • PTPRO protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3