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Garofalo A Giai C Lattar S Gardella N Mollerach M Kahl BC Becker K Prince AS Sordelli DO Gómez MI 《The Journal of infectious diseases》2012,206(1):81-90
Staphylococcus aureus protein A (SpA) plays a critical role in the induction of inflammation. This study was aimed to determine whether the number of short sequence repeats (SSRs) present in the polymorphic region modulates the inflammatory response induced by SpA. We demonstrated that there is a dose-response effect in the activation of interferon (IFN)-β signaling in airway epithelial and immune cells, depending on the number of SSRs, which leads to differences in neutrophil recruitment. We also determined that a significant proportion of isolates from patients with chronic infections such as osteomyelitis and cystic fibrosis carry fewer SSRs than do isolates from patients with acute infections or healthy carriers and that there was an inverse correlation between the number of SSRs and the length of disease course. Given the importance of IFN signaling in eradication of S. aureus, loss of SSRs may represent an advantageous mechanism to adapt to and persist in the host. 相似文献
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Greco E Quintiliani G Santucci MB Serafino A Ciccaglione AR Marcantonio C Papi M Maulucci G Delogu G Martino A Goletti D Sarmati L Andreoni M Altieri A Alma M Caccamo N Di Liberto D De Spirito M Savage ND Nisini R Dieli F Ottenhoff TH Fraziano M 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(21):E1360-E1368
We have generated unique asymmetric liposomes with phosphatidylserine (PS) distributed at the outer membrane surface to resemble apoptotic bodies and phosphatidic acid (PA) at the inner layer as a strategy to enhance innate antimycobacterial activity in phagocytes while limiting the inflammatory response. Results show that these apoptotic body-like liposomes carrying PA (ABL/PA) (i) are more efficiently internalized by human macrophages than by nonprofessional phagocytes, (ii) induce cytosolic Ca(2+) influx, (iii) promote Ca(2+)-dependent maturation of phagolysosomes containing Mycobacterium tuberculosis (MTB), (iv) induce Ca(2+)-dependent reactive oxygen species (ROS) production, (v) inhibit intracellular mycobacterial growth in differentiated THP-1 cells as well as in type-1 and -2 human macrophages, and (vi) down-regulate tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β, IL-18, and IL-23 and up-regulate transforming growth factor (TGF)-β without altering IL-10, IL-27, and IL-6 mRNA expression. Also, ABL/PA promoted intracellular killing of M. tuberculosis in bronchoalveolar lavage cells from patients with active pulmonary tuberculosis. Furthermore, the treatment of MTB-infected mice with ABL/PA, in combination or not with isoniazid (INH), dramatically reduced lung and, to a lesser extent, liver and spleen mycobacterial loads, with a concomitant 10-fold reduction of serum TNF-α, IL-1β, and IFN-γ compared with that in untreated mice. Altogether, these results suggest that apoptotic body-like liposomes may be used as a Janus-faced immunotherapeutic platform to deliver polar secondary lipid messengers, such as PA, into phagocytes to improve and recover phagolysosome biogenesis and pathogen killing while limiting the inflammatory response. 相似文献
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Manetti M Allanore Y Saad M Fatini C Cohignac V Guiducci S Romano E Airó P Caramaschi P Tinazzi I Riccieri V Della Rossa A Abbate R Caporali R Cuomo G Valesini G Dieudé P Hachulla E Cracowski JL Tiev K Letenneur L Amouyel P Lambert JC Chiocchia G Martinez M Ibba-Manneschi L Matucci-Cerinic M 《Annals of the rheumatic diseases》2012,71(6):1034-1041
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Verma S Tachtatzis P Penrhyn-Lowe S Scarpini C Jurk D Von Zglinicki T Coleman N Alexander GJ 《Hepatology (Baltimore, Md.)》2012,56(4):1510-1520
Telomeres, a validated biomarker of aging, comprise multiple nucleotide repeats capping chromosomes that shorten with each cell cycle until a critical length is achieved, precipitating cell senescence. Only two previous studies focused on the effect of aging in "normal" liver tissue, but these studies were compromised by small sample size, limited age range, tissue derived from individuals with an increased risk of senescence, and the use of liver homogenates. We developed a robust large-volume, four-color quantitative fluorescent in situ hybridization technique to measure telomere length in large numbers of hepatocytes, Kupffer cells, hepatic stellate cells, CD4-positive and CD8-positive lymphocytes, and cholangiocytes. Following validation against the gold standard (Southern blotting), the technique was applied to normal archived paraffin-embedded liver tissue obtained following reperfusion of implanted donor liver. We studied 73 highly selected donors aged 5-79 years with a short medical illness preceding death and no history of liver disease, reperfusion injury, or steatosis and normal graft function 1-year posttransplantation. Cholangiocytes had significantly longer telomeres compared with all other intrahepatic lineages over a wide age range (P < 0.05). Age-related telomere attrition was restricted to sinusoidal cells (i.e., Kupffer cells [P = 0.0054] and stellate cells [P = 0.0001]). Cholangiocytes and hepatocytes showed no age-related telomere shortening. Conclusion: In normal liver and over a broad age range, cholangiocytes have longer telomeres than all other intrahepatic lineages. Age-related telomere length decline is restricted to Kupffer cells and stellate cells. (HEPATOLOGY 2012). 相似文献
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Antonio Preti Ileana Usai Elisa Pintus Cinzia Sardu Donatella Rita Petretto Carmelo Masala 《Laterality》2013,18(3):318-339
Handedness has been linked to an enhanced risk of alcohol abuse, while less is known about other drugs. A convenience sample of 1004 male and female Italian participants (females=58%) from the general community (18 to 65 years old: average age = 30; standard deviation = 10, median = 25) was asked about: handedness (preference in writing); lifetime use of alcohol, tobacco, and illicit drugs; levels of psychological distress, as measured by the General Health Questionnaire (GHQ); and levels of delusion proneness, as measured by the Peters et al. Delusions Inventory (PDI). Overall, 92 individuals (9.2%) were classified as left-handed, with no significant difference reported among genders. Lifetime use of illicit drugs, primarily cannabis, was reported by 20% of the sample. In a multiple logistic regression analysis, after taking into account sex, age, and caseness on GHQ and PDI, left-handed people in the sample were statistically more likely to report lifetime experimentation with heroin, ecstasy/amphetamine, and, marginally, hallucinogens, but not alcohol or tobacco. Different mechanisms might contribute to an explanation of greater lifetime experimentation with some illicit drugs among left-handed people as compared to right-handed people. However, replications with clinical samples are necessary before any definitive statements can be made. 相似文献
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Elena Arrigoni Laura de Girolamo Alessia Di Giancamillo Deborah Stanco Claudia Dellavia Davide Carnelli Marino Campagnol Cinzia Domeneghini Anna T. Brini 《Journal of orthopaedic science》2013,18(2):331-339