Chunjie Han

Angiotensin II induces C-reactive protein expression through ERK1/2 and JNK signaling in human aortic endothelial cells.

BACKGROUND Atherosclerosis is an inflammatory disease in the vessel. As an inflammatory cytokine, C-reactive protein (CRP) participates in atherogenesis. Although angiotensin II (AngII) is known to evoke inflammatory response in vascular endothelial cells (VECs), there is no direct evidence to demonstrate the proinflammatory effect of AngII on VECs through CRP. The present study focused on effect of AngII on CRP expression and the signal pathway in human aortic endothelial cells (HAECs). METHODS AND RESULTS mRNA and protein expression was identified by RT-PCR and Western blot, respectively. Reactive oxygen species (ROS) were observed by a fluorescence microscope. The results showed that AngII significantly increased mRNA and protein expression of CRP in HAECs in time- and concentration-dependent ways. Anti-IL-1beta and anti-IL-6 neutralizing antibodies did not affect AngII-induced CRP expression. Losartan reduced AngII-induced CRP expression in mRNA and protein levels in HAECs. Losartan and TIFA decreased AngII-stimulated ROS generation, and antioxidant NAC completely abolished AngII-induced CRP expression in HAECs. The further study indicated that losartan, NAC, PD98059, SP600125 significantly inhibited ERK1/2 and JNK phosphorylation, and PD98059, SP600125, PDTC completely antagonized AngII-induced CRP expression in HAECs. CONCLUSIONS The present study demonstrates that AngII has ability to induce CRP expression in HAECs through AT(1)-ROS-ERK1/2 and JNK-NF-kappaB signal pathway, which strengthens understanding of the proinflammatory and proathroscerotic actions of AngII.

Epigallocatechin-3-gallate inhibits angiotensin II and interleukin-6-induced C-reactive protein production in macrophages

BACKGROUND Consumption of green tea has been associated with health benefits against multiple diseases including cardiovascular diseases. However, the action mechanisms of green tea and its major ingredient epigallocatechin-3-gallate (EGCG) against cardiovascular diseases are still unclear. Emerging evidence has suggested a common role for C-reactive protein (CRP) in the pathogenesis of inflammation and atherosclerosis. Therefore, the effect of EGCG on angiotensin II (Ang II)- and interleukin-6 (IL-6)-induced CRP production in U937 macrophages and the possible mechanisms were observed. METHODS U937 macrophages were cultured, and Ang II and IL-6 were used as stimulants for generation of CRP. U937 macrophages were preincubated with EGCG at 1, 3, 10 μM for 1 h prior to the stimulation. mRNA expression and protein level were determined by RT-PCR and ELISA, respectively. ROS production was observed by a fluorescence microscope. RESULTS Pretreatment of macrophages with EGCG prior to the stimulation concentration-dependently inhibited Ang II- and IL-6-induced expression of CRP both in protein and mRNA levels. Meanwhile, EGCG reduced Ang II- and IL-6-stimulated generation of ROS in macrophages. CONCLUSION EGCG is able to inhibit Ang II- and IL-6-stimulated CRP expression in macrophages to produce an anti-inflammation by interfering with ROS generation. The finding is helpful to update understanding of anti-atherosclerotic effects of EGCG.

Nicotine induces the expression of C-reactive protein via MAPK-dependent signal pathway in U937 macrophages.

Atherosclerosis is an inflammatory disease in the vessel wall. Nicotine, a major component of cigarette smoke, is an independent risk factor for cardiovascular diseases including atherosclerosis. As an inflammatory molecule, C- reactive protein (CRP) participates in atherogenesis. Although it has been confirmed that CRP level in smoking patient is significantly higher than non-smokers and cigarette withdrawal, it is unknown whether nicotine induces CRP expression in macrophages. The present study was to observe effect of nicotine on CRP production and the related signal pathway in U937 macrophages. The results showed that nicotine significantly increased mRNA and protein expression of CRP in U937 macrophages in time- and concentration-dependent ways. Nicotinic acetylcholine receptor (nAChR) blocker hexamethonium, MEK1/2 inhibitor PD98059, p38 MAPK inhibitor SB203580 and NF-κB inhibitor PDTC almost completely abolished nicotineinduced CRP expression in mRNA and protein levels in U937 macrophages. The further study indicated that hexamethonium, PD98059, and SB203580 significantly inhibited ERK1/2 and p38 MAPK phosphorylation. These demonstrate that nicotine has ability to induce CRP expression in macrophages through nAChR-ERK1/2/p38 MAPK-NF-κB signal pathway, which contributes to better understanding of the pro-inflammatory and pro-atherosclerotic effects of nicotine in cigarette smokers.

Angiotensin II induces the expression of c-reactive protein via MAPK-dependent signal pathway in U937 macrophages.

Atherosclerosis is an inflammatory disease in the vessel wall. As an inflammatory molecule, C-reactive protein (CRP) participates in all stages of atherosclerotic process. Although angiotensin II (Ang II) can stimulate the vascular cells to produce CRP, it is unknown whether Ang II induces CRP expression in macrophages. The present study was to observe effect of Ang II on CRP production and the related signal pathway in U937 macrophages so as to provide more evidence for the proinflammatory action of Ang II. The results showed that Ang II significantly increased mRNA and protein expression of CRP in U937 macrophages in time- and concentration-dependent manners. AT1 receptor blocker losartan blocked Ang II -induced CRP expression in mRNA and protein levels in U937 macrophages. Losartan and complex II inhibitor TIFA decreased Ang II -stimulated reactive oxygen species (ROS) generation, and antioxidant NAC completely abolished Ang II -induced CRP expression in U937 macrophages. The further study indicated that losartan, NAC, MEK1/2 inhibitor PD98059, p38MAPK inhibitor SB203580 obviously inhibited ERK1/2 and p38MAPK phosphorylation, and PD98059, SB203580 and NF-ĸB inhibitor PDTC reduced Ang II -induced mRNA and protein expression of CRP in U937 macrophages. These demonstrate that Ang II is capable of inducing CRP generation in macrophages via AT1-ROS-ERK1/2/p38MAPK-NF-ĸB signal pathway, which contributes to better understanding of the proinflammatory and proatherosclerotic actions of Ang II.

Lovastatin Reduces Apoptosis and Downregulates the CD40 Expression Induced by TNF-α in Cerebral Vascular Endothelial Cells

Inflammation may be one of the independent risk factors contributing to many neurological diseases. Moreover, there is an emerging body of data indicating that statins may have neuroprotective action. Recent studies suggest that CD40-CD40 ligand (CD40L) system is proven to be an important mediator of several auto-immune and chronic inflammation diseases. To address whether lovastatin produces neuroprotection as a potential novel anti-inflammatory pathway through the inhibition of CD40 expression, we examined the possible effects of lovastatin on expression of CD40, apoptosis, level of nitric oxide (NO) and nitric oxide synthase (NOS) activity induced by tumor necrosis factor alpha (TNF-alpha) in the cerebral vascular endothelial cells (CVECs) involved in cerebrovascular diseases. Preincubation with lovastatin (10(-7), 10(-6) and 10(-5) mol/l) for 24 hours (h) protected CVECs from TNF-alpha-induced decrease of cellular viability. Further, lovastatin inhibited the TNF-alpha-induced increases of NO level, NOS activity, apoptotic cells and CD40 expression in a dose-dependent manner, and anti-CD40 antibody also inhibited the cellular apoptosis induced by TNF-alpha. In conclusion, our data provide evidence to support a direct pro-inflammatory effect of CD40-CD40L signaling pathway in CVECs, and lovastatin possesses an anti-inflammatory effect independent of its lipid-lowering action involved in the cerebrovascular diseases.