A Novel Role for Interleukin-18 in Adhesion Molecule Induction through NFκB and Phosphatidylinositol (PI) 3-Kinase-dependent Signal Transduction Pathways

Morel, Jacques; Park, Christy C.; Woods, James M.; Koch, Alisa E.

doi:10.1074/jbc.m103574200

Cited by 153 publications

(124 citation statements)

References 41 publications

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“…In fact, it was demonstrated that culture supernatants from DENV infected primary human monocytes could activate endothelial cells by eliciting expression of VCAM-1 and ICAM-1 in these cells (Anderson et al 1997). Interestingly, the IL-18 plasma levels were positively correlated with sICAM-1 levels together with the expression of CD54 on T CD8 cells, as described previously that IL-18 increases the expression of ICAM-1 (Morel et al 2001) and VCAM-1 (Vidal- Vanaclocha et al 2000), enhancing the recruitment of lymphocytes into inflammatory tissues. Furthermore, our study revealed that CD8 + T cells expressing HLA-DR were significantly present in higher frequency in Severe Dengue cases.…”

Section: Table IIImentioning

confidence: 61%

“…In addition, levels of IL-18 have been directly correlated with soluble ICAM-1 in plasma and also with CD8 T cells expressing ICAM-1 (Table III). In fact, previous data demonstrated that IL-18 increases the expression of adhesion molecules ICAM-1 and VCAM-1 (Morel et al 2001), which facilitate the emigration of neutrophils and lymphocytes in containing a nidus of infection, thereby contributing to the primary process in inflammatory diseases.…”

Section: Correlation Between Il-18 With Soluble and Surface Icam And mentioning

confidence: 99%

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Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease

Azeredo¹,

Zagne

Alvarenga³

et al. 2006

Mem. Inst. Oswaldo Cruz

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Section: Table IIImentioning

confidence: 61%

Section: Correlation Between Il-18 With Soluble and Surface Icam And mentioning

confidence: 99%

Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease

Azeredo¹,

Zagne

Alvarenga³

et al. 2006

Mem. Inst. Oswaldo Cruz

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“…Quiescent cardiomyocytes were treated with IL-18 for 1 h. Cytoplasmic and nuclear protein extracts were analyzed for GSK3␤ levels by Western blotting. (32). Therefore, we analyzed PI3K activation following IL-18 treatment by PI3K lipid kinase assays.…”

Section: Il-18 Induces Cardiomyocyte Hypertrophy-il-18 Signals Via Ilmentioning

confidence: 99%

Interleukin-18 Is a Pro-hypertrophic Cytokine That Acts through a Phosphatidylinositol 3-Kinase-Phosphoinositide-dependent Kinase-1-Akt-GATA4 Signaling Pathway in Cardiomyocytes

Chandrasekar

Mummidi

Claycomb

et al. 2005

Journal of Biological Chemistry

117

113

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In patients with congestive heart failure, high serum levels of the proinflammatory cytokine interleukin (IL)-18 were reported. A positive correlation was described between serum IL-18 levels and the disease severity. IL-18 has also been shown to induce atrial natriuretic factor (ANF) gene expression in adult cardiomyocytes. Because re-expression of the fetal gene ANF is mostly associated with hypertrophy, a hallmark of heart failure, we hypothesized that IL-18 induces cardiomyocyte hypertrophy. Treatment of the cardiomyocyte cell line HL-1 with IL-18 induced hypertrophy as characterized by increases in protein synthesis, phosphorylated p70 S6 kinase, and ribosomal S6 protein levels as well as cell surface area. Furthermore, IL-18 induced ANF gene transcription in a time-dependent manner as evidenced by increased ANF secretion and ANF promoter-driven reporter gene activity. Investigation into possible signal transduction pathways mediating IL-18 effects revealed that IL-18 activates phosphoinositide 3-kinase (PI3K), an effect that was blocked by wortmannin and LY-294002. IL-18 induced Akt phosphorylation and stimulated its activity, effects that were abolished by Akt inhibitor or knockdown. IL-18 stimulated GATA4 DNA binding activity and increased transcription of a reporter gene driven by multimerized GATA4-binding DNA elements. Pharmacological inhibition or knockdown studies revealed that IL-18 induced cardiomyocyte hypertrophy and ANF gene transcription via PI3K, PDK1, Akt, and GATA4. Most importantly, IL-18 induced ANF gene transcription and hypertrophy of neonatal rat ventricular myocytes via PI3K-, Akt-, and GATA4-dependent signaling. Together these data provide the first evidence that IL-18 induces cardiomyocyte hypertrophy via PI3K-dependent signaling, defines a mechanism of IL-18-mediated ANF gene transcription, and further supports a role for IL-18 in inflammatory heart diseases including heart failure.

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“…A possible explanation for the reduced recruitment of ␣␤ T cells to the target tissue could be an altered expression of adhesion molecules due to the functional inactivation of IL-18 during CHS. As reported earlier, IL-18 enhances the expression of VCAM-1, ICAM-1, and E-selectin on endothelial cells (37). The up-regulation of VCAM-1 on hepatic sinusoidal endothelium by IL-18 has been implicated in hepatic melanoma metastasis (38).…”

Section: Discussionmentioning

confidence: 64%

IL-18 Binding Protein Protects Against Contact Hypersensitivity

Plitz¹,

Saint-Mézard

Satho

et al. 2003

The Journal of Immunology

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Allergic contact dermatitis, the clinical manifestation of contact hypersensitivity, is one of the most common disorders of the skin. It is elicited upon multiple cutaneous re-exposure of sensitized individuals to the sensitizing agent. In this study, we demonstrate that using IL-18 binding protein (IL-18BP) to neutralize IL-18 significantly reduced clinical symptoms in a murine model of contact hypersensitivity. Furthermore, IL-18BP alleviated the relapses during established disease, as indicated by significant protection during re-exposure of mice that had previously undergone a contact hypersensitivity response without treatment. Although edema was not influenced, IL-18BP reduced the number of T cells homing to sites of inflammation, resulting in diminished local production of IFN-γ. Thus, by preventing the accumulation of effector T cells to the target tissue, IL-18BP appears to be a potent protective mediator to counter skin inflammation during contact hypersensitivity. Taken together with the evidence that IL-18 is present in tissue samples of the human disease, our data reinforces IL-18BP as a candidate for this therapeutic indication.

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A Novel Role for Interleukin-18 in Adhesion Molecule Induction through NFκB and Phosphatidylinositol (PI) 3-Kinase-dependent Signal Transduction Pathways

Abstract: Interleukin-18 (IL-18

Cited by 153 publications

References 41 publications

Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease

Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease

Interleukin-18 Is a Pro-hypertrophic Cytokine That Acts through a Phosphatidylinositol 3-Kinase-Phosphoinositide-dependent Kinase-1-Akt-GATA4 Signaling Pathway in Cardiomyocytes

IL-18 Binding Protein Protects Against Contact Hypersensitivity

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