Interleukin-1beta (IL-1beta) stimulates expression of the highly inducible enzyme cyclooxygenase-2 (COX-2) via activation of nuclear factor kappaB (NFkappaB), and consequently provokes prostaglandin E(2) (PGE(2)) synthesis, which induces inflammatory responses. In this study, the contribution of protein kinase C (PKC) to IL-1beta-induced PGE(2) synthesis in human gingival fibroblasts was invest...

Following induction and activation of the early growth response (Egr)-1 transcription factor in human chondrocytes, interleukin-1beta (IL-1beta) suppresses the expression of the type II collagen gene (COL2A1), associated with induction of Egr-1 binding activity in nuclear extracts. The COL2A1 proximal promoter contains overlapping binding sites for Egr-1 and Sp1 family members at -119/-112 bp a...

OBJECTIVES To explore the source of the p19 subunit of interleukin-23 (IL-23) in joints with rheumatoid arthritis (RA), the effects of IL-1beta and tumour necrosis factor (TNF)-alpha on IL-23 gene expression in RA fibroblast-like synoviocytes and the effect of IL-23 on proinflammatory cytokines. METHODS Expression of IL-23 p19 in joints was examined by immunohistochemical analysis of patients...

Interleukin-1beta (IL-1beta) represents one of the most important mediators of inflammation and host responses to infection. Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, induces IL-1beta secretion at the site of infection, but the underlying mechanism(s) are poorly understood. In this work we show that Mtb infection of macrophages stimulates caspase-1 activity an...

BACKGROUND Inflammation is important in atherogenesis. Interleukin (IL)-1 is the prototypic inflammatory cytokine. We hypothesized a dysbalance between inflammatory and anti-inflammatory mediators in the IL-1 family in coronary artery disease (CAD) and a possible modulation of these mediators by HMG-CoA inhibitors (statins). METHODS AND RESULTS In a microarray screening experiment examining p...

OBJECTIVE Cytokine-induced hepatic serum amyloid A (SAA) synthesis is the critical step in the pathogenesis of AA amyloidosis secondary to rheumatoid arthritis (RA). This study was conducted to provide more insight into the mechanism of SAA production in hepatocytes and its regulation. METHODS Primary cultured normal human hepatocytes were stimulated with cytokines (IL-1beta, TNF-alpha and IL...

Caspase-1, the prototypic caspase, is known to process the cytokines IL-1beta and IL-18 to mature forms but it is unclear whether, like other caspases, it can induce apoptosis by activation of downstream protease cascades. Neutrophils are known to express caspase-1, to release IL-1beta and to undergo rapid, caspase-dependent apoptosis. We examined apoptosis and IL-1beta production in peripheral...

Staphylococcus (S.) aureus is an important pathogen causing various infections including those of the skin. Keratinocytes are able to sense invading S. aureus and to initiate a fast defense reaction by the rapid release of innate defense mediators such as antimicrobial peptides and cytokines. There is increasing evidence that the cytokines IL-1alpha and IL-1beta, which both signal through the I...

IL-1beta has been shown to play a pivotal role in the development of inflammatory disorders. We recently found that a natural triterpene, ursolic acid (UA), enhanced MIF release from nonstimulated macrophages. In this study, we examined the effects of UA on the production of several cytokines in resident murine peritoneal macrophages (pMphi). UA increased the protein release of IL-1beta, IL-6, ...

IL-1beta and IL-18 are crucial mediators of inflammation, and a defective control of their release may cause serious diseases. Yet, the mechanisms regulating IL-1beta and IL-18 secretion are partially undefined. Both cytokines are produced as inactive cytoplasmic precursors. Processing to the active form is mediated by caspase-1, which is in turn activated by the multiprotein complex inflammaso...