Expression and regulation of inducible IkappaB kinase (IKK-i) in human fibroblast-like synoviocytes

Cellular Immunology
K R AupperleG S Firestein

Abstract

IkappaB kinase (IKK) plays a key role in the regulation of nuclear factor kappaB (NF-kappaB). We previously demonstrated the expression of two kinases, IKK1 and IKK2, in fibroblast-like synoviocytes (FLS) and determined their functional consequences for inflammatory gene expression in vitro and in vivo. Recently, a novel inducible IkappaB kinase has been described, namely, IKK-i or IKK-epsilon, which is functionally and structurally distinct from constitutively expressed IKK1 and IKK2. Therefore, we investigated the expression and regulation of this novel kinase in FLS from patients with rheumatoid arthritis and osteoarthritis. Interestingly, constitutive gene expression and protein expression were observed in all cell lines examined. TNFalpha stimulation for 24 h increased IKK-i expression 7.2 +/- 1.8-fold in FLS (P < 0.02). IL-1 also significantly increased IKK-i gene expression. Time course experiments demonstrated that IKK-i gene expression increased within 3 h of TNFalpha stimulation and persisted for at least 24 h. Dose-response studies showed that as little as 1 ng/ml of TNFalpha increased IKK-i gene expression. Constitutive IKK-1 gene expression was also noted in rheumatoid arthritis, osteoarthritis, and normal synovium...Continue Reading

Citations

Apr 2, 2005·Nature Reviews. Drug Discovery·Heike A WielandKarl A Rudolphi
May 29, 2009·Annals of the Rheumatic Diseases·Akihisa FukushimaGary S Firestein
Oct 9, 2003·Annals of the Rheumatic Diseases·D HammakerG S Firestein
Jan 21, 2014·Autoimmunity·Abdullah Alghasham, Zafar Rasheed
Sep 26, 2006·Bioorganic & Medicinal Chemistry Letters·Paul BamboroughLisa M Shewchuk
Feb 12, 2004·Arthritis and Rheumatism·Huang-Ge ZhangJohn D Mountz
Apr 23, 2004·Current Opinion in Rheumatology·Susan E Sweeney, Gary S Firestein
Jun 19, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ellen Niederberger, Gerd Geisslinger
Aug 5, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine V MöserEllen Niederberger
Mar 1, 2007·Arthritis and Rheumatism·Susan E SweeneyGary S Firestein
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Valérie DevauchelleGilles Chiocchia
May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Susan E SweeneyGary S Firestein
Mar 31, 2009·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Jiangnan HuangMei Yu

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.