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IL-18 Expression (il-18 + expression)

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Medical Sciences	100%

Selected Abstracts

Interleukin 18 causes hepatic ischemia/reperfusion injury by suppressing anti-inflammatory cytokine expression in mice

HEPATOLOGY, Issue 3 2004
Dan Takeuchi
Hepatic ischemia/reperfusion injury is a clinically important problem. While the mechanisms of the initial event and subsequent neutrophil-dependent injury are somewhat understood, little is known about the regulation of endogenous hepatoprotective effects on this injury. Interleukin 12 (IL-12) plays a role in the induction of this injury, but involvement of interleukin 18 (IL-18) has not been clarified. Using a murine model of partial hepatic ischemia and subsequent reperfusion, the aim of the current study was to determine whether IL-18 is up-regulated during hepatic ischemia/reperfusion and to determine the role of endogenous IL-18 in the development and regulation of inflammatory hepatic ischemia/reperfusion injury. Hepatic IL-18 expression was up-regulated from 1 to 8 hours after reperfusion. Hepatic ischemia/reperfusion induced nuclear factor-,B (NF-,B) and activator protein 1 (AP-1) activation, as defined by electrophoretic mobility shift assay, and caused significant increases in liver neutrophil recruitment, apoptosis, hepatocellular injury, and liver edema as defined by liver myeloperoxidase content, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) staining, serum aminotransferase levels, and liver wet-to-dry weight ratios. In mice treated with neutralizing antibody to IL-18, ischemia/reperfusion-induced increases in CXC chemokine expression, activation of NF-,B and AP-1, and apoptosis were greatly reduced. Furthermore, under blockade of IL-18, anti-inflammatory cytokines such as IL-4 and IL-10 were greatly up-regulated. Signal transducer and activator of transcription 6 (STAT6) was significantly activated under blockade of IL-18. These conditions also caused significant reduction in liver neutrophil sequestration and liver injury. In conclusion, the data suggest that IL-18 is required for facilitating neutrophil-dependent hepatic ischemia/reperfusion injury through suppressing anti-inflammatory cytokine expression. (HEPATOLOGY 2004;39:699,710.) [source]

Effects of interleukin 18 on injury and activation of human proximal tubular epithelial cells

NEPHROLOGY, Issue 1 2007
DONG LIANG
SUMMARY: Background/Aims: Injury and activation of tubular proximal epithelial cells (TEC) play central roles in renal tubulointerstitial fibrosis (TIF), but its mechanisms remain obscure. Interleukin 18 (IL-18) is overproduced during chronic kidney diseases (CKD), but how IL-18 affects the biological behaviour of TEC is not clear. The aim of the present study is to reveal the role of IL-18 in renal TIF. Methods: The expressions of IL-18 and IL-18 receptor in TEC were detected by immunohistochemical staining in vivo and by reverse transcriptase polymerase chain reaction (RT-PCR) in vitro. TEC line (HK-2 cells) were incubated without or with IL-18. Cell proliferation and cell cycle were evaluated by methyl thiazolyl tetrazolium assay and flow cytometric analysis, respectively. Cell apoptosis was assessed by Hoechst 33258 staining. Expression of ,-smooth muscle actin was evaluated by RT-PCR, immunocytochemical staining and flow cytometric analysis, respectively. Type I collagen, fibronectin, MCP-1 and RANTES in cultured supernatants were measured by enzyme-linked immunosorbent assay. Results: IL-18 expression in TEC increased significantly in CKD state. IL-18 receptor was constitutively expressed in normal proximal TEC, and its expression increased strongly in CKD state. Proliferation and cell cycle of HK-2 cells were not affected by IL-18. Cell apoptosis, ,-smooth muscle actin expression, type I collagen and fibronectin production as well as MCP-1 secretion were promoted by IL-18 in dosage- and/or time-dependent manners, but RANTES secretion was not affected. Conclusion: IL-18 may play a crucial role in the process of TIF by promoting TEC injury and activation, and could be a target of the therapeutic approaches against TIF. [source]

Association of interleukin-18 expression with enhanced levels of both interleukin-1, and tumor necrosis factor , in knee synovial tissue of patients with rheumatoid arthritis

ARTHRITIS & RHEUMATISM, Issue 2 2003
Leo A. B. Joosten
Objective To examine the expression patterns of interkeukin-18 (IL-18) in synovial biopsy tissue of patients with rheumatoid arthritis (RA), and to determine whether expression of this primary cytokine is related to the expression of other cytokines and adhesion molecules and related to the degree of joint inflammation. Methods Biopsy specimens of knee synovial tissue either without synovitis (n = 6) or with moderate or severe synovitis (n = 11 and n = 12, respectively) were obtained from 29 patients with active RA. Paraffin-embedded, snap-frozen sections were used for immunohistochemical detection of IL-18, tumor necrosis factor , (TNF,), IL-1,, IL-12, and IL-17. Furthermore, adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin, and cell markers CD3, CD14, and CD68 were stained. Results IL-18 staining was detectable in 80% of the RA patients, in both the lining and sublining of the knee synovial tissue. IL-18 expression in the synovial tissue was strongly correlated with the expression of IL-1, (in the sublining r = 0.72, in the lining r = 0.71; both P < 0.0001) and TNF, (in the sublining r = 0.59, P < 0.0007, and in the lining r = 0.68, P < 0.0001). In addition, IL-18 expression in the sublining correlated with macrophage infiltration (r = 0.64, P < 0.0007) and microscopic inflammation scores (r = 0.78, P < 0.0001), and with the acute-phase reaction as measured by the erythrocyte sedimentation rate (r = 0.61, P < 0.0004). Interestingly, RA synovial tissue that coexpressed IL-18 and IL-12 demonstrated enhanced levels of the Th1-associated cytokine IL-17. Conclusion Our results show that expression of IL-18 is associated with that of IL-1, and TNF, and with local inflammation in the synovial tissue of patients with RA. In addition, synovial IL-18 expression correlates with the acute-phase response. These data indicate that IL-18 is a primary proinflammatory cytokine in RA that drives the local production of IL-1, and TNF,. [source]