Beta-adrenergic stimulation induces interleukin-18 expression via beta2-AR, PI3K, Akt, IKK, and NF-kappaB.

We investigated whether beta-adrenergic receptor (beta-AR) stimulation induces the expression of interleukin (IL)-18, a proinflammatory cytokine, in myocardium and in cardiac-derived endothelial cells (CDEC) via activation of nuclear factor (NF)-kappaB. Our results indicate that isoproterenol (ISO) activates NF-kappaB DNA binding activity, and induces myocardial and systemic elaboration of IL-18 via beta2-AR signaling. Furthermore, in CDEC, ISO increased basal and inducible promoter activities, increased IL-18 gene transcription and mRNA stability, and induced IL-18 expression via beta2-AR agonism.

CXCL16 signals via Gi, phosphatidylinositol 3-kinase, Akt, I kappa B kinase, and nuclear factor-kappa B and induces cell-cell adhesion and aortic smooth muscle cell proliferation.

CXCL16, a recently discovered transmembrane chemokine, is expressed in human aortic smooth muscle cell (ASMC). It facilitates uptake of low density lipoproteins by macrophages, resulting in foam cell formation. However, it is not known whether ASMC express CXCR6, the receptor for CXCL16, or whether CXCL16 affects ASMC biology.

Fractalkine (CX3CL1) stimulated by nuclear factor kappaB (NF-kappaB)-dependent inflammatory signals induces aortic smooth muscle cell proliferation through an autocrine pathway.

Fractalkine (also known as CX3CL1), a CX3C chemokine, activates and attracts monocytes/macrophages to the site of injury/inflammation. It binds to CX3C receptor 1 (CX3CR1), a pertussis toxin-sensitive G-protein-coupled receptor. In smooth muscle cells (SMCs), fractalkine is induced by proinflammatory cytokines [tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)], which may mediate monocyte adhesion to SMCs.