Casein kinase 2-interacting protein-1, an inflammatory signaling molecule interferes with TNF reverse signaling in human model cells

Kata Juhász, A. Zvara, Anna Maria Lipp, Benedikt Nimmervoll, Alois Sonnleitner, Zsolt Balogi, E. Duda

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

When transmembrane form of tumor necrosis factor (mTNF) interacts with its cognate receptors or agonistic antibodies signaling pathways are activated in the ligand expressing cells. This "reverse signaling" appears a fine-tuning control mechanism in the immune response. Despite a clinical relevance key molecules of TNF reverse signaling and their functions remain elusive. We examined the role of CKIP-1, an interacting partner of the N terminal fragment of mTNF in inflammation and TNF reverse signaling. We found that CKIP-1 expression was elevated upon LPS challenge in THP-1 human monocyte model cells. Overexpression of CKIP-1 triggered classical activation of THP-1 cells and transactivated the human TNF promoter when co-expressed with c-Jun in the HEK293 model system. TNF reverse signaling induced a massive translocation of CKIP-1 from the plasma membrane to intracellular compartments in THP-1 cells. Expression of the N terminal fragment of mTNF in HEK293 cells resembled the effects of TNF reverse signaling with respect to relocalization of CKIP-1. In parallel with the translocation, CKIP-1-triggered activation of THP-1 cells was antagonized by TNF reverse signaling. Similarly, the presence of the N terminal fragment of mTNF inhibited CKIP-1 mediated TNF promoter activation in HEK293 cells. Both TNF reverse signaling in THP-1 cells and expression of the N terminal fragment of mTNF in HEK293 cells were found to induce apoptosis that could be prevented by overexpression of CKIP-1. Our findings demonstrate that CKIP-1 activates pro-inflammatory pathways and interferes with TNF reverse signaling induced apoptosis in human model cells.

Original languageEnglish
Pages (from-to)55-64
Number of pages10
JournalImmunology Letters
Volume152
Issue number1
DOIs
Publication statusPublished - Apr 2013

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Casein Kinase II
HEK293 Cells
Proteins
Apoptosis
Monocytes
Tumor Necrosis Factor-alpha
Cell Membrane
Ligands
Inflammation
Antibodies

Keywords

  • CKIP-1
  • Infliximab
  • Monocytes
  • Reverse signaling
  • Transmembrane TNF

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Casein kinase 2-interacting protein-1, an inflammatory signaling molecule interferes with TNF reverse signaling in human model cells. / Juhász, Kata; Zvara, A.; Lipp, Anna Maria; Nimmervoll, Benedikt; Sonnleitner, Alois; Balogi, Zsolt; Duda, E.

In: Immunology Letters, Vol. 152, No. 1, 04.2013, p. 55-64.

Research output: Contribution to journalArticle

Juhász, Kata ; Zvara, A. ; Lipp, Anna Maria ; Nimmervoll, Benedikt ; Sonnleitner, Alois ; Balogi, Zsolt ; Duda, E. / Casein kinase 2-interacting protein-1, an inflammatory signaling molecule interferes with TNF reverse signaling in human model cells. In: Immunology Letters. 2013 ; Vol. 152, No. 1. pp. 55-64.
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