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

Juhász, Katalin and Zvara, Ágnes and Lipp, Anna-Maria and Balogi, Zsolt and Duda, Ernő (2013) Casein kinase 2-interacting protein-1, an inflammatory signaling molecule interferes with TNF reverse signaling in human model cells. Immunology Letters, 152 (1). pp. 55-64. ISSN 0165-2478

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Abstract

When transmembrane form of tumor necrosis factor (mTNF) interacts with its cognate receptors or agonistic antibodies signaling pathways are activated in the ligaud 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. (C) 2013 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: APOPTOSIS; ALPHA; B-CELLS; IFN-GAMMA; RHEUMATOID-ARTHRITIS; MONOCYTIC CELLS; PLASMA-MEMBRANE; T-CELLS; PLECKSTRIN HOMOLOGY DOMAIN; infliximab; TRANSMEMBRANE TNF; reverse signaling; MONOCYTES; CKIP-1
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 07 Nov 2013 15:15
Last Modified: 07 Nov 2013 15:15
URI: http://real.mtak.hu/id/eprint/7185

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