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P043. PRKCDBP, a new transcriptional target of TNF-alpha signaling pathway in ulcerative colitis

H.J. Kim1, C.K. Lee1, K.H. Kang1, 1Kyung Hee University Hospital, Internal Medicine, Seoul, South Korea

Background

PRKCDBP is a proapoptotic tumor suppressor and its gene expression is directly activated by NF-kB in response to TNF-alpha which plays a crucial role in colonic inflammation and tumorigenesis. Nevertheless, TNF-alpha/PRKCDBP signaling pathways has never been examined in human inflammatory bowel disease. The aim of this study was to evaluate the correlation between the expression of PRKCDBP and TNF-alpha proteins by using immunohistochemistry pre and post-IFX (infliximab) therapy and analyzed in patients with moderate to severe UC (ulcerative colitis).

Methods

The 31 patients (13 female; median age, 41 years) with moderate to severe UC received IFX were included. Tissue samples used in immunohistochemistry were therapy naïve 31 biopsy samples from patients and 26 biopsy samples obtained after IFX therapy in these patients. Immunohistochemical staining with antibody against TNF-alpha and PRKCDBP was performed on all biopsies and expressed as immunoreactive score was obtained by the percentage of cells with staining intensity.

Results

There was significant correlation in their immunoreactivity. IFX therapy reduced the immunohistochemical expression of TNF-alpha and PRKCDBP (p = 0.003 and p < 0.001, respectively). Mean expression level of TNF-alpha dropped from 56.2% to 36.2%, and PRKCDBP from 56.2% to 30.2%. And, the level of immunohistochemical expression of pre- and post-therapy PRKCDBP correlated significantly with pre- and post-therapy TNF-alpha (Spearman rank correlation test; p = 0.002 and p = 0.006, respectively).

Conclusion

These results demonstrated for the first time that mucosal expression of PRKCDBP is strongly correlated with TNF-alpha in patients with moderate to severe UC. Furthermore, a profound down-regulation of PRKCDBP and TNF-alpha appeared to be associated with anti-inflammtory effect of IFX. These results suggested that PRKCDBP could be the new transcriptional target of TNF-alpha signaling pathway in ulcerative colitis. Thus, PRKCDBP could be as a new possible therapeutic target for inflammatory bowel disease. Further studies at the RNA level are suggested.