Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells.

BACKGROUND: Microglial activation plays an important role in neurodegenerative diseases through production of nitric oxide (NO) and several pro-inflammatory cytokines. Lipoxins (LXs) and aspirin-triggered LXs (ATLs) are considered to act as 'braking signals' in inflammation. In the present study, we investigated the effect of aspirin-triggered LXA4 (ATL) on infiammatory responses induced by lipopolysaccharide (LPS) in murine microglial BV-2 cells. METHODS: BV-2 cells were treated with ATL prior to LPS exposure, and the effects of such treatment production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß) and tumour necrosis factor-α (TNF-α) were analysed by Griess reaction, ELISA, western blotting and quantitative RT-PCR. Moreover, we investigated the effects of ATL on LPS-induced nuclear factor-κB (NF-κB) activation, phosphorylation of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) activation. RESULTS: ATL inhibited LPS-induced production of NO, IL-1ß and TNF-α in a concentration-dependent manner. mRNA expressions for iNOS, IL-1ß and TNF-α in response to LPS were also decreased by ATL. These effects were inhibited by Boc-2 (a LXA4 receptor antagonist). ATL significantly reduced nuclear translocation of NF-κB p65, degradation of the inhibitor IκB-α, and phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK in BV-2 cells activated with LPS. Furthermore, the DNA binding activity of NF-κB and AP-1 was blocked by ATL. CONCLUSIONS: This study indicates that ATL inhibits NO and pro-inflammatory cytokine production at least in part via NF-κB, ERK, p38 MAPK and AP-1 signaling pathways in LPS-activated microglia. Therefore, ATL may have therapeutic potential for various neurodegenerative diseases.

Transmission of SARS in three Chinese hospitals.

OBJECTIVE: To quantify the transmissibility of severe acute respiratory syndrome (SARS) in hospitals in mainland China and to assess the effectiveness of control measures. METHODS: We report key epidemiological details of three major hospital outbreaks of SARS in mainland China, and estimate the evolution of the effective reproduction number in each of the three hospitals during the course of the outbreaks. RESULTS: The three successive hospital outbreaks infected 41, 99 and 91 people of whom 37%, 60% and 70% were hospital staff. These cases resulted in 33 deaths, five of which occurred in hospital staff. In a multivariate logistic regression, age and whether or not the case was a healthcare worker (HCW) were found to be significant predictors of mortality. The estimated effective reproduction numbers (95% CI) for the three epidemics peaked at 8 (5, 11), 9 (4, 14) and 12 (7, 17). In all three hospitals the epidemics were rapidly controlled, bringing the reproduction number below one within 25, 10 and 5 days respectively. CONCLUSIONS: This work shows that in three major hospital epidemics in Beijing and Tianjin substantially higher rates of transmission were initially observed than those seen in the community. In all three cases the hospital epidemics were rapidly brought under control, with the time to successful control becoming shorter in each successive outbreak.

Geographical spread of SARS in mainland China.

OBJECTIVES: To describe the spatiotemporal diffusion of the severe acute respiratory syndrome (SARS) epidemic in mainland China, and to analyse the spatial pattern of SARS transmission from the Beijing epicentre to its neighbouring areas. METHODS: Probable SARS cases occurring between November 2002 and May 2003 in mainland China were compiled from different sources and geo-coded into a geographical information database based on onset location. Spatial analyses including kernel density estimation, and spatial statistical and tracking analyses were performed to characterise the spatiotemporal distribution of SARS cases based on onset location/date. SARS cases that got infected in Beijing but were reported in three provinces surrounding Beijing were mapped, and logistic regression using a 'case-control' design at the county level was performed to analyse the impact of travel-related risk factors in the diffusion pattern. RESULTS: The SARS epidemic in mainland China spanned a large geographical extent but clustered in two areas: first in Guangdong Province, and about 3 months later in Beijing with its surrounding areas in Shanxi Province, Inner Mongolia Autonomic Region, Hebei Province and Tianjin. Counties in the neighbourhood of Beijing that were crossed by a national highway or inter-provincial freeway showed the highest risk of acquiring SARS infections, even after correction for population density and medical staff density. Being intersected by a railway did not significantly associate with risk of SARS. CONCLUSIONS: This study provides the first complete documentation of the spatial and temporal characteristics of the SARS epidemic in mainland China. Our analyses confirmed that SARS had benefited from national highways and inter-provincial freeways for its spread from epicentres to neighbouring areas, whereas trains showed no significant association. This knowledge may be important for the control of re-emerging SARS, or other future emerging human-to-human transmittable infections.

Effect of ciliary neurotrophic factor on activation of astrocytes in vitro.

Objective To observe the activating effect of ciliary neurotrophic factor (CNTF) on astrocyte in vitro. Methods Astrocytes cultured purely from newborn rats. Cerebral cortex was raised in normal and serum deprivation condition with different concentrations (in ng/ml: 0, 2, 20, or 200) of CNTF. After cultured for 24 h, the shape and the cell cycle of astrocytes were examined by immunocytochemistry and flow cytometer, respectively. Results The immunoactivity of glial fibrillary acidic protein (GFAP) and the nuclear size of astrocytes were increased when CNTF was applied, whether cells were cultured in medium with or without serum. CNTF promoted astrocytes to enter the cell cycle in medium with serum, but had no this effect in medium without serum. Conclusion In medium without serum, astrocytes could differentiate into activated state cells with CNTF application, but could not proliferate; in medium with serum, astrocytes could proliferate with aid of CNTF.