Cigarette smoke increases TLR4 and TLR9 expression and induces cytokine production from CD8+ T cells in chronic obstructive pulmonary disease

Background

Cigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder. COPD is characterized by an increase in CD8⁺ T cells within the central and peripheral airways. We hypothesized that the CD8⁺ T cells in COPD patients have increased Toll-like receptor (TLR) expression compared to control subjects due to the exposure of cigarette smoke in the airways.

Methods

Endobronchial biopsies and peripheral blood were obtained from COPD patients and control subjects. TLR4 and TLR9 expression was assessed by immunostaining of lung tissue and flow cytometry of the peripheral blood. CD8⁺ T cells isolated from peripheral blood were treated with or without cigarette smoke condensate (CSC) as well as TLR4 and TLR9 inhibitors. PCR and western blotting were used to determine TLR4 and TLR9 expression, while cytokine secretion from these cells was detected using electrochemiluminescence technology.

Results

No difference was observed in the overall expression of TLR4 and TLR9 in the lung tissue and peripheral blood of COPD patients compared to control subjects. However, COPD patients had increased TLR4 and TLR9 expression on lung CD8⁺ T cells. Exposure of CD8⁺ T cells to CSC resulted in an increase of TLR4 and TLR9 protein expression. CSC exposure also caused the activation of CD8⁺ T cells, resulting in the production of IL-1β, IL-6, IL-10, IL-12p70, TNFα and IFNγ. Furthermore, inhibition of TLR4 or TLR9 significantly attenuated the production of TNFα and IL-10.

Conclusions

Our results demonstrate increased expression of TLR4 and TLR9 on lung CD8⁺ T cells in COPD. CD8⁺ T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production. These results provide a new perspective on the role of CD8⁺ T cells in COPD.     

Chemical characterization and antimicrobial activity of rhizome essential oils of very closely allied Zingiberaceae species endemic to Borneo: Alpinia ligulata K. Schum. and Alpinia nieuwenhuizii Val

Two poorly studied, morphologically allied Alpinia species endemic to Borneo, viz., A. ligulata and A. nieuwenhuizii, were investigated here for their rhizome essential oil. The oil compositions and antimicrobial activities were compared with those of A. galanga, a better known plant. A fair number of compounds were identified in the oils by GC‐FID and GC/MS analyses, with large differences in the oil composition between the three species. The rhizome oil of A. galanga was rich in 1,8‐cineole (29.8%), while those of A. ligulata and A. nieuwenhuizii were both found to be extremely rich in (E)‐methyl cinnamate (36.4 and 67.8%, resp.). The three oils were screened for their antimicrobial activity against three Gram‐positive and three Gram‐negative bacteria and two fungal species. The efficiency of growth inhibition of Staphylococcus aureus var. aureus was found to decline in the order of A. nieuwenhuizii>A. ligulata ～ A. galanga, while that of Escherichia coli decreased in the order of A. galanga>A. nieuwenhuzii ～ A. ligulata. Only the A. galanga oil inhibited the other bacteria and the fungi tested.     

Changes in the plant proteome resulting from salt stress: toward the creation of salt-tolerant crops?

Salinity in agricultural land is a major problem worldwide, placing a severe constraint on crop growth and productivity in many regions, and increased salinization of arable land is expected to have devastating global effects. Though plants vary in their sensitivity to salt stress, high salinity causes water deficit and ion toxicity in many plant species. Considerable efforts have therefore been made to investigate how genes respond to salt stress in various plants by using several approaches, including proteomics. Proteomic approaches for identifying proteins that are regulated in response to salt stress are becoming common in the post-genomics era of crop research. In this review, we describe the physiological and biological changes in the proteomes of several important food crops under salt stress. We also provide a viewpoint into how proteomics-based research is likely to develop in this field.     

Cladophialophora psammophila, a novel species of Chaetothyriales with a potential use in the bioremediation of volatile aromatic hydrocarbons

Cladophialophora is a genus of asexual black yeast-like fungi with one-celled, hydrophobic conidia which is predicted to have teleomorphs in the ascomycete genus Capronia, a member of the order Chaetothyriales. Cladophialophora species are relatively frequently involved in human disease ranging from mild cutaneous lesions to cerebral abscesses. Although the natural niche outside humans is unknown for most opportunistic Cladophialophora species, the fungi concerned are rarely isolated from environmental samples such as dead plant material, rotten wood, or soil. The objective of the present paper is to describe a novel species of Cladophialophora which was isolated from soil polluted with benzene, toluene, ethylbenzene, and xylene (BTEX). It proved to be able to grow with toluene and other related alkylbenzenes as its sole carbon and energy source. This strain is of interest for the biodegradation of toluene and other related xenobiotics under growth limiting conditions, particularly in air biofilters, dry and/or acidic soil. A preliminary genetic analysis using multilocus sequencing typing (MLST) and amplified fragments length polymorphism (AFLP) showed that this fungus was closely related to the pathogenic species Cladophialophora bantiana, sharing a C. bantiana-specific intron in SSU rDNA. However, it was unable to grow at 40°C and proved to be non-virulent in mice. The clear phylogenetic and ecophysiological delimitation of the species is fundamental to prevent biohazard in engineered bioremediation applications.     

Age shall not weary us: deleterious effects of self-regulation depletion are specific to younger adults

Self-regulation depletion (SRD), or ego-depletion, refers to decrements in self-regulation performance immediately following a different self-regulation-demanding activity. There are now over a hundred studies reporting SRD across a broad range of tasks and conditions. However, most studies have used young student samples. Because prefrontal brain regions thought to subserve self-regulation do not fully mature until 25 years of age, it is possible that SRD effects are confined to younger populations and are attenuated or disappear in older samples. We investigated this using the Stroop color task as an SRD induction and an autobiographical memory task as the outcome measure. We found that younger participants (<25 years) were susceptible to depletion effects, but found no support for such effects in an older group (40-65 years). This suggests that the widely-reported phenomenon of SRD has important developmental boundary conditions casting doubt on claims that it represents a general feature of human cognition.     

Renal thrombotic microangiopathy in mice with combined deletion of endocytic recycling regulators EHD3 and EHD4

Eps15 Homology Domain-containing 3 (EHD3), a member of the EHD protein family that regulates endocytic recycling, is the first protein reported to be specifically expressed in the glomerular endothelium in the kidney; therefore we generated Ehd3(-/-) mice and assessed renal development and pathology. Ehd3(-/-) animals showed no overt defects, and exhibited no proteinuria or glomerular pathology. However, as the expression of EHD4, a related family member, was elevated in the glomerular endothelium of Ehd3(-/-) mice and suggested functional compensation, we generated and analyzed Ehd3(-/-); Ehd4(-/-) mice. These mice were smaller, possessed smaller and paler kidneys, were proteinuric and died between 3-24 weeks of age. Detailed analyses of Ehd3(-/-); Ehd4(-/-) kidneys demonstrated thrombotic microangiopathy (TMA)-like glomerular lesions including thickening and duplication of glomerular basement membrane, endothelial swelling and loss of fenestrations. Other changes included segmental podocyte foot process effacement, mesangial interposition, and abnormal podocytic and mesangial marker expression. The glomerular lesions observed were strikingly similar to those seen in human pre-eclampsia and mouse models of reduced VEGF expression. As altered glomerular endothelial VEGFR2 expression and localization and increased apoptosis was observed in the absence of EHD3 and EHD4, we propose that EHD-mediated endocytic traffic of key surface receptors such as VEGFR2 is essential for physiological control of glomerular function. Furthermore, Ehd3(-/-); Ehd4(-/-) mice provide a unique model to elucidate mechanisms of glomerular endothelial injury which is observed in a wide variety of human renal and extra-renal diseases.     

Assessment of factors influencing morale in the elderly

Background

We examined the relationship between morale measured by the Philadelphia Geriatric Morale Scale (PGC) and disability, social support, religiosity, and personality traits. Instruments predicting morale were then tested against PGC domains.

Methods

The study utilized a cross-sectional survey with a multistage cluster sampling design. Instruments used were disability (disease burden; WHO Disability Score-II, WHODAS-II), social support (Duke Social Support Scale, DUSOCS; Lubben Social Network Scale, LSNS-6; Medical Outcomes Study Social Support Survey, MOS-SSS), religiosity (Revised Intrinsic-Extrinsic Religious Orientation Scale, I/E-R), and personality (Ten-Item Personality Inventory, TIPI). These were plotted as bar charts against PGC, resolved with one-way ANOVA and Kruskal-Wallis tests, then corrected for multiple comparisons. This process was repeated with PGC domains. Contribution of factors was modeled using population attributable risk (PAR) and odds ratios. Effect of confounders such as gender, age, and ethnicity were checked using binary logistic regression.

Results

All instruments showed clear relationships with PGC, with WHODAS-II and DUSOCS performing well (ANOVA p<0.001). For PGC domains, attitude toward aging and lonely dissatisfaction trended together, while agitation did not. PAR, odds ratios, and Exp(β) were disability (WHODAS-II: 28.5%, 3.8, 2.8), social support (DUSOCS: 28.0%, 3.4, 2.2), religiosity (I/E-R: 21.6%, 3.2, 2.1), and personality (TIPI: 27.9%, 3.6, 2.4). Combined PAR was 70.9%.

Conclusions

Disability, social support, religiosity, and personality strongly influence morale in the elderly. WHODAS-II and DUSOCS perform best in measuring disability and social support respectively.     

A fear-inducing odor alters PER2 and c-Fos expression in brain regions involved in fear memory

Evidence demonstrates that rodents learn to associate a foot shock with time of day, indicating the formation of a fear related time-stamp memory, even in the absence of a functioning SCN. In addition, mice acquire and retain fear memory better during the early day compared to the early night. This type of memory may be regulated by circadian pacemakers outside of the SCN. As a first step in testing the hypothesis that clock genes are involved in the formation of a time-stamp fear memory, we exposed one group of mice to fox feces derived odor (TMT) at ZT 0 and one group at ZT 12 for 4 successive days. A separate group with no exposure to TMT was also included as a control. Animals were sacrificed one day after the last exposure to TMT, and PER2 and c-Fos protein were quantified in the SCN, amygdala, hippocampus, and piriform cortex. Exposure to TMT had a strong effect at ZT 0, decreasing PER2 expression at this time point in most regions except the SCN, and reversing the normal rhythm of PER2 expression in the amygdala and piriform cortex. These changes were accompanied by increased c-Fos expression at ZT0. In contrast, exposure to TMT at ZT 12 abolished the rhythm of PER2 expression in the amygdala. In addition, increased c-Fos expression at ZT 12 was only detected in the central nucleus of the amygdala in the TMT12 group. TMT exposure at either time point did not affect PER2 or c-Fos in the SCN, indicating that under a light-dark cycle, the SCN rhythm is stable in the presence of repeated exposure to a fear-inducing stimulus. Taken together, these results indicate that entrainment to a fear-inducing stimulus leads to changes in PER2 and c-Fos expression that are detected 24 hours following the last exposure to TMT, indicating entrainment of endogenous oscillators in these regions. The observed effects on PER2 expression and c-Fos were stronger during the early day than during the early night, possibly to prepare appropriate systems at ZT 0 to respond to a fear-inducing stimulus.