The NF-kappa B target genes ICAM-1 and VCAM-1 are differentially regulated during spontaneous differentiation of Caco-2 cells

Astarci, Erhan
Sade, Asli
Cimen, Ismail
Banerjee, Sreeparna
Intestinal epithelial differentiation entails the formation of highly specialized cells with specific absorptive, secretory, digestive and immune functions. Cellcell and cellmicroenvironment interactions appear to be crucial in determining the outcome of the differentiation process. Using the Caco-2 cell line, which undergoes spontaneous re-differentiation when grown past confluency, we observed a loss of VCAM-1 (vascular cell adhesion molecule 1) mRNA expression, while ICAM-1 (intercellular cell adhesion molecule 1) mRNA expression was seen to increase over the course of differentiation. Protein kinase C? (PKC?) acted downstream of protein kinase Ca (PKCa) to inactivate inhibitor of ?B (I?B) and activate nuclear factor ?B (NF-?B) in undifferentiated cells, and this pathway was inhibited in the differentiated cells. The increase in ICAM-1 mRNA expression in the differentiated cells was due to increased promoter recruitment of C/EBP beta, which transcriptionally up-regulated ICAM-1 mRNA. However, protein expression of ICAM-1 was found to decrease over the course of differentiation due to degradation in the proteasome and lysosome. Immunohistochemistry using tumor samples from colon cancer patients indicated that non-transformed matched normal cells (well-differentiatied) showed no ICAM-1 expression, but the poorly differentiated tumor cells showed higher expression. Functionally, a decrease in adhesion to human umbilical vein endothelial cells was observed in the differentiated Caco-2 cells. Thus, regulation of ICAM-1 and VCAM-1, although both NF-?B target genes, appears to be different over the course of epithelial differentiation in Caco-2 cells.


Drug repositioning as an effective therapy for protease-activated receptor 2 inhibition
Saqib, Uzma; Savai, Rajkumar; Liu, DongFang; Banerjee, Sreeparna; Baig, Mirza S. (Wiley, 2019-02-01)
Proteinase-activated receptor 2 (PAR-2) is a G protein-coupled receptor activated by both trypsin and a specific agonist peptide, SLIGKV-NH2. It has been linked to various pathologies, including pain and inflammation. Several peptide and peptidomimetic agonizts for PAR-2 have been developed exhibiting high potency and efficacy. However, the number of PAR-2 antagonists is smaller. We screened the Food and Drug Administration library of approved compounds to retrieve novel antagonists for repositioning in the...
Immunotherapeutic applications of CpG ODN
Gürsel, Mayda (2006-06-01)
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs stimulate the mammalian immune system to mount a rapid innate immune response. This response is characterized by the production of polyreactive IgM, immunomodulatory cytokines and chemokines. CpG ODN directly stimulate lymphocytes, natural killer cells and professional antigen-presenting cells (such as macrophages and dendritic cells). Owing to the strength and nature of this stimulation, CpG ODN are being harnessed f...
The effect of cysteine-43 mutation on thermostability and kinetic properties of citrate synthase from Thermoplasma acidophilum
Kocabıyık, Semra; Russel, RJM; Danson, MJ; Hough, DW (Elsevier BV, 1996-07-05)
In this study, we have substituted serine-43 by cysteine in the recombinant citrate synthase from a moderately thermophilic Archaeon Thermoplasma acidophilum, for site-specific attachment of labels and have investigated the effects of this mutation on the biochemical properties and thermal stability of the enzyme. Both wild-type and the mutant enzymes were purified to homogenity using affinity chromatography on Matrex Gel Red A. The mutant Thermoplasma citrate synthase is very similar to wild-type citrate s...
Structural Insights into Alternate Aggregated Prion Protein Forms
POLANO, maurizio; Bek, Alpan; BENETTİ, federico; lazzarino, marco; LEGNAME, giuseppe (Elsevier BV, 2009-11-13)
The conversion of the cellular form of the prion protein (PrPC) to an abnormal, alternatively folded isoform (PrPSc) is the central event in prion diseases or transmissible spongiform encephalopathies. Recent studies have demonstrated de novo generation of murine prions from recombinant prion protein (recPrP) after inoculation into transgenic and wild-type mice. These so-called synthetic prions lead to novel prion diseases with unique neuropathological and biochemical features. Moreover, the use of recPrP i...
Butyrate mediated regulation of RNA binding proteins in the post-transcriptional regulation of inflammatory gene expression
Torun, Aydan; Enayat, Shabnam; Sheraj, Ilir; Tuncer, Sinem; Ulgen, Dogukan Hazar; Banerjee, Sreeparna (Elsevier BV, 2019-12-01)
Short chain fatty acids (SCFAs) are produced by commensal bacteria in the gut and are known to reduce inflammation through transcriptional inhibition of cytokines and inflammatory proteins such as cyclooxygenase-2 (COX-2). Butyrate is a SCFA that was reported to alter the mRNA stability of inflammatory genes by increasiing the expression of the RNA binding protein (RBP) Tristetraprolin (TTP). We have hypothesized that butyrate may regulate gene expression post-transcriptionally through global effects on the...
Citation Formats
E. Astarci, A. Sade, I. Cimen, B. SAVAŞ, and S. Banerjee, “The NF-kappa B target genes ICAM-1 and VCAM-1 are differentially regulated during spontaneous differentiation of Caco-2 cells,” FEBS JOURNAL, pp. 2966–2986, 2012, Accessed: 00, 2020. [Online]. Available: