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Increased levels of NF-κB inhibitors (IκBα and IκBγ) in the intestinal mucosa of Crohn's disease patients during infliximab treatment

TitoloIncreased levels of NF-κB inhibitors (IκBα and IκBγ) in the intestinal mucosa of Crohn's disease patients during infliximab treatment
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2005
AutoriGuidi, L., Costanzo Mario, Ciarniello M., De Vitis I., Pioli Claudio, Gatta L., Pace L., Tricerri A., Bartoloni C., Coppola L., Balistreri P., Doria G., Fedeli G., and Gasbarrini G.B.
RivistaInternational Journal of Immunopathology and Pharmacology
Volume18
Paginazione155-164
ISSN03946320
Parole chiaveadult, aged, Antibodies, antiinflammatory activity, article, Blotting, cell stimulation, clinical article, controlled study, Crohn disease, cytokine production, drug effect, drug efficacy, drug infusion, drug mechanism, Female, follow up, Gastrointestinal Agents, human, human cell, human tissue, Humans, I kappa B alpha, I kappa B beta, I-kappa B Proteins, immunoglobulin enhancer binding protein, immunohistochemistry, inflammatory cell, infliximab, Intestinal Mucosa, intestine biopsy, intestine mucosa, leukocyte culture, lipopolysaccharide, male, Middle Aged, Monoclonal, Monocytes, NF-kappa B, parameter, Peptide Fragments, peripheral blood mononuclear cell, phytohemagglutinin, prediction, priority journal, protein determination, protein function, protein induction, supernatant, tissue level, transcription factor RelA, Transcription Factors, tumor necrosis factor alpha, Tumor Necrosis Factor-alpha, Western, Western blotting
Abstract

The treatment with infliximab is employed successfully in Crohn's disease (CD) but predictors of efficacy are lacking. Activation of the transcription factor NF-kB has been demonstrated in CD and its inhibition is one of the mechanisms by which anti-inflammatory agents exert their effects. We evaluated the production of TNFα by peripheral blood mononuclear cells (PBMC) and the levels of NF-κB family molecules in the intestinal mucosa during infliximab therapy in 12 patients. TNFα was assayed on supernatants of PBMC culture stimulated with PHA or LPS. Immunohistochemistry was also done on intestinal biopsies. In six patients, Western blot analysis of the NF-kB subunit Rel-A, and its inhibitors IκBα and IκBγ was performed on intestinal biopsies and PBMC. The TNFα production by LPS stimulated PBMC showed mild changes, while it was increased by PHA-stimulated PBMC after treatment. The number of inflammatory cells in the intestinal mucosa was reduced (p<0.002) by the treatment. In five out of six cases we detected an increase of the IκBα and IκBγ inhibitor levels in intestinal biopsies after treatment. An increase of IκB inhibitors levels could be one of the mechanisms by which infliximab decreases NF-κB activity and exerts its anti-inflammatory effects.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-20044386118&partnerID=40&md5=2c0f2a29970e37e77174267c1c0a8abe
Citation KeyGuidi2005155