Atherosclerosis is a chronic inflammatory disease; unstable atherosclerotic plaque rupture, vascular stenosis, or occlusion caused by platelet aggregation and thrombosis lead to acute cardiovascular disease. Atherosclerosis-related inflammation is mediated by proinflammatory cytokines, inflammatory signaling pathways, bioactive lipids, and adhesion molecules. This review discusses the effects of inflammation and the systemic inflammatory signaling pathway on atherosclerosis, the role of related signaling pathways in inflammation, the formation of atherosclerosis plaques, and the prospects of treating atherosclerosis by inhibiting inflammation.

Overexpression of calbindin-D(28k) (CaBP-28 k) induces neurite outgrowth in dopaminergic neuronal cells and could provide some protection to dopaminergic neurons against the pathological process in Parkinson's disease. Transgenic mice CaBP-28 k overexpression and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models were generated, and the effect of midbrain dopamine neurons in ethology was also assessed. Tyrosine hydroxylase (TH)-immunoreactive neurons were counted, and the concentration of total protein and dopamine (DA) of striatum corpora was measured in four animal models. Results showed that the positive TH cells, content of DA, and ability of ethology in MPTP-induced transgenic mice were significantly higher than that in MPTP-induced wild-type mice. The findings demonstrate that overexpression of CaBP-28 k could provide protection for DA neurons from neurodegeneration. It would provide a potential strategy in the treatment of Parkinson's diseases.

Growth factors like insulin-like growth factor 1 (IGF-1) is reported to mediate neurogenesis in the subgranular zone (SGZ) and the subventricular zone (SVZ) of the adult mammalian brain, but its regulatory mechanism remains unclear. We generated transgenic mice overexpressing IGF-1 specifically in neural stem cells (NSCs) and assessed the effect of IGF-1 on neurogenesis in adult mice NSCs. Overexpression of IGF-1 could stimulate the expression of phospho-Akt and phospho-ERK1/2 while inducing proliferation and differentiation of NSCs in the SGZ and SVZ. The MEK/ERK inhibitor U0126 could inhibit ERK1/2 phosphorylation, further inhibiting the proliferation of NSCs in the SGZ and SVZ but had no effect on the phosphorylation of Akt. By contrast, The PI3K/Akt inhibitor LY294002 inhibited phosphorylation of Akt and differentiation of NSCs in the SGZ and SVZ, resulting in no change in the proliferation of NSCs and ERK1/2 phosphorylation. These results demonstrate that IGF-1 upregulates the proliferation of NSCs by triggering MEK/ERK pathway signaling in the adult mice SGZ and SVZ. Meanwhile, IGF-1 also induces differentiation of NSCs via the PI3K/Akt pathway in adult mice. However, we found no evidence of crosstalk between the PI3K/Akt and MEK/ERK pathways in adult mice NSCs. Our work provides new experimental evidence of the involvement of the PI3K/Akt and MEK/ERK pathways in the proliferation and differentiation of the NSCs of adult mice.

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Heme oxygenase (HO) represents an intrinsic antiinflammatory system based on its ability to inhibit expression of proinflammatory cytokines. The constitutive isoform heme oxygenase-2 (HO-2) has high expression and activity in cerebral microvascular endothelial cells (CMVEC). This study was undertaken to evaluate the role of HO-2 in regulation of TLR4/MyD88-dependent signaling and to study the effect of HO-2 on the expression and secretion of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and Interleukin-6 (IL6) in CMVEC. HO-2 short hairpin RNA (shRNA) and HO-2 overexpression plasmids were used to observe the effect of HO-2 on proinflammatory cytokines in CMVEC in vitro, and the results showed that the messenger RNA (mRNA) and protein levels of TNF-α and IL6 were increased and decreased, respectively, compared with control groups. LPS-stimulated TNF-α and IL6 mRNA and protein were also reduced in CMVEC treated with an inhibitor of TLR4 signaling, CLI-095, or HO-2 overexpression. CLI-095 and HO-2 overexpression both reduced TLR4 expression in CMVEC, and HO-2 shRNA blocked these effects of CLI-095. CLI-095 and HO-2 overexpression potently suppressed TLR4/MyD88-dependent proinflammatory cytokine expression in CMVEC. These results suggest that HO-2 plays an important role in protecting CMVEC against cytokine-mediated inflammation.