Elevation of PRKCDBP, A Novel Transcriptional Target of TNF-α, and Its Downregulation by Infliximab in Patients with Ulcerative Colitis

Jung Wook Kim, Hyo Jong Kim, Chang Kyun Lee, Jae Jun Shim, Jae Young Jang, Suk Ho Dong, Byung Ho Kim, Young Woon Chang, Sung-Gil Chi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Protein kinase C delta binding protein (PRKCDBP/Cavin3/hSRBC) is a putative tumor suppressor that is downregulated in many human cancers. Recently, PRKCDBP was identified to be activated by nuclear factor-κB in response to tumor necrosis factor (TNF)-α.

Aims: To explore the potential of PRKCDBP as a diagnostic or prognostic marker for inflammatory bowel disease, the possible correlation between its expression status and TNF-α signaling was evaluated in ulcerative colitis (UC) patients, both pre- and post-infliximab (IFX) therapy.

Methods: In total, 31 IFX therapy-naïve patients (13 females; median age, 41 years) with moderate-to-severe UC who had been scheduled for IFX treatment were included. Immunohistochemical analysis of TNF-α and PRKCDBP expression was performed in rectal biopsies.

Results: A significant correlation was observed in immunoreactivity between TNF-α and PRKCDBP. IFX therapy reduced immunohistochemical expression of PRKCDBP and TNF-α (P < 0.001 and P = 0.005, respectively). The mean PRKCDBP expression level decreased from 54.5 to 30.2 %, and that of TNF-α decreased from 54.5 to 36.2 %. The immunohistochemical expression pre- and post-PRKCDBP therapy correlated significantly with TNF-α levels pre- and post-therapy (Spearman’s rank correlation test; P = 0.005 and P = 0.001, respectively).

Conclusions: These results demonstrate that mucosal expression of PRKCDBP correlated strongly with TNF-α expression in UC patients and that IFX therapy resulted in profound reductions in both PRKCDBP and TNF-α. Thus, these findings support that PRKCDBP expression is tightly controlled by TNF-α, and the anti-inflammatory effect of IFX may in part stem from blockade of the TNF-α-PRKCDBP signaling pathway.

Original languageEnglish
Pages (from-to)2947-2957
Number of pages11
JournalDigestive Diseases and Sciences
Volume59
Issue number12
DOIs
Publication statusPublished - 2014 Jan 1

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Keywords

  • Immunohistochemistry
  • Infliximab
  • PRKCDBP
  • Tumor necrosis factor-alpha
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

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