title: Elevation of PRKCDBP, a novel transcriptional target of TNF-α, and its downregulation by infliximab in patients with ulcerative colitis.
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.
  
  
  OBJECTIVE
  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.
authors: Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University School of Medicine, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul, 130-872, Republic of Korea.
authors: Jung-Wook
authors: JW
authors: Kim
authors: Hyo Jong
authors: HJ
authors: Kim
authors: Chang Kyun
authors: CK
authors: Lee
authors: Jae-Jun
authors: JJ
authors: Shim
authors: Jae Young
authors: JY
authors: Jang
authors: Suk Ho
authors: SH
authors: Dong
authors: Byung-Ho
authors: BH
authors: Kim
authors: Young Woon
authors: YW
authors: Chang
authors: Sung-Gil
authors: SG
authors: Chi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D000069285:Infliximab; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; C505360:CAVIN3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab