Impact of IL-1ß on lung pathology caused by Mycobacterium abscessus infection and its association with IL-17 production.

Mycobacterium abscessus (MAB), a non-tuberculous mycobacterium (NTM), causes chronic pulmonary inflammation in humans. The NLRP3 inflammasome is a multi-protein complex that triggers IL-1ß maturation and pyroptosis through the cleavage of caspase-1. In this study, we investigated the roles of NLRP3 and IL-1ß in the host's defense against MAB. The IL-1ß production by MAB was completely abolished in NLRP3, but not NLRC4, deficient macrophages. The NLRP3 inflammasome components, which are ASC and caspase-1 were also found to be essential for IL-1ß production in response to MAB. NLRP3 and IL-1ß deficiency did not affect the intracellular growth of MAB in macrophages, and the bacterial burden in lungs of NLRP3- and IL-1ß-deficient mice was also comparable to the burden observed in WT mice. In contrast, IL-1ß deficiency ameliorated lung pathology in MAB-infected mice. Notably, the lung homogenates of IL-1ß-deficient mice had reduced levels of IL-17, but not IFN-γ and IL-4 when compared with WT counterparts. Furthermore, in vitro co-culture analysis showed that IL-1ß signaling was essential for IL-17 production in response to MAB. Finally, we observed that the anti-IL-17 antibody administration moderately mitigated MAB-induced lung pathology. These findings indicated that IL-1ß production contribute to MAB-induced lung pathology via the elevation of IL-17 production.

Water Extract of Desalted Salicornia europaea Inhibits RANKL-Induced Osteoclast Differentiation and Prevents Bone Loss in Ovariectomized Mice.

Osteoporosis, which is often associated with increased osteoclast activity due to menopause or aging, was the main focus of this study. We investigated the inhibitory effects of water extract of desalted Salicornia europaea L. (WSE) on osteoclast differentiation and bone loss in ovariectomized mice. Our findings revealed that WSE effectively inhibited RANKL-induced osteoclast differentiation, as demonstrated by TRAP staining, and also suppressed bone resorption and F-actin ring formation in a dose-dependent manner. The expression levels of genes related to osteoclast differentiation, including NFATc1, ACP5, Ctsk, and DCSTAMP, were downregulated by WSE. Oral administration of WSE improved bone density and structural parameters in ovariectomized mice. Dicaffeoylquinic acids (DCQAs) and saponins were detected in WSE, with 3,4-DCQA, 3,5-DCQA, and 4,5-DCQA being isolated and identified. All tested DCQAs, including the aforementioned types, inhibited osteoclast differentiation, bone resorption, and the expression of osteoclast-related genes. Furthermore, WSE and DCQAs reduced ROS production mediated by RANKL. These results indicate the potential of WSE and its components, DCQAs, as preventive or therapeutic agents against osteoporosis and related conditions.

A Low-Cost Lightweight Deflectometer with an Arduino-Based Signal Interpretation Kit to Evaluate Soil Modulus.

This research presents an innovative solution aimed at addressing the cost and accessibility challenges associated with soil stiffness analysis in construction projects. Traditional lightweight deflectometer (LWD) systems have limitations due to their high cost and proprietary nature, prompting the need for a more widely accessible technology. To fulfill this purpose, a low-cost, open-source LWD onboard sensor signal interpretation system, utilizing Electro-Mechanical and Micro-Electro-Mechanical-System (MEMS) technology-based sensors in conjunction with an Arduino® Uno and ADS1262 Breakout Board, has been developed. This system efficiently processes raw signal data into deflection and force units, enabling precise soil property analysis. Thorough enhancements, calibration, and alignment procedures have been applied and validated through field tests, which have produced highly satisfactory results. By significantly reducing costs while maintaining accuracy, this developed system has the potential to popularize quality control and assurance practices in the construction industry. This open-source approach not only enhances affordability but also broadens accessibility, making soil property analysis more efficient and attainable for a wider range of construction projects.

One-Step Passivation of Both Sulfur Vacancies and SiO2 Interface Traps of MoS2 Device.

Transition metal dichalcogenides (TMDs) benefit electrical devices with spin-orbit coupling and valley- and topology-related properties. However, TMD-based devices suffer from traps arising from defect sites inside the channel and the gate oxide interface. Deactivating them requires independent treatments, because the origins are dissimilar. This study introduces a single treatment to passivate defects in a multilayer MoS2 FET. By applying back-gate bias, protons from an H-TFSI droplet are injected into the MoS2, penetrating deeply enough to reach the SiO2 gate oxide. The characterizations employing low-temperature transport and deep-level transient spectroscopy (DLTS) studies reveal that the trap density of S vacancies in MoS2 drops to the lowest detection level. The temperature-dependent mobility plot on the SiO2 substrate resembles that of the h-BN substrate, implying that dangling bonds in SiO2 are passivated. The carrier mobility on the SiO2 substrate is enhanced by approximately 2200% after the injection.

TSS Removal Efficiency and Permeability Degradation of Sand Filters in Permeable Pavement.

Permeable pavement is a highly effective technology in Low-Impact Development (LID) for managing stormwater runoff, which helps mitigate environmental impacts. Filters are essential components of permeable pavement systems as they prevent permeability reduction, remove pollutants, and enhance the system's overall efficiency. This research paper focuses on exploring the influence of three factors, including total suspended solids (TSS) particle size, TSS concentration, and hydraulic gradient, on the permeability degradation and TSS removal efficiency of sand filters. A series of tests were conducted using different values of these factors. The results demonstrate that these factors have an influence on permeability degradation and TSS removal efficiency (TRE). A larger TSS particle size results in higher permeability degradation and TRE than a smaller particle size. Higher TSS concentrations lead to higher permeability degradation and lower TRE. Additionally, smaller hydraulic gradients are associated with higher permeability degradation and TRE. However, the influence of TSS concentration and hydraulic gradient seems less significant than that of TSS particle size for the values of the factors considered in the tests. In summary, this study provides valuable insights into the effectiveness of sand filters in permeable pavement and identifies the main factors that influence permeability degradation and TRE.

Oral Administration of Lactobacillus sakei CVL-001 Improves Recovery from Dextran Sulfate Sodium-Induced Colitis in Mice by Microbiota Modulation.

Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory disease, and its incidence is steadily increasing. IBD is closely related to the intestinal microbiota, and probiotics are known to be a potential therapeutic agent for IBD. In our study, we evaluated the protective effect of Lactobacillus sakei CVL-001, isolated from Baechu kimchi, on dextran sulfated sodium (DSS)-induced colitis in mice. The oral administration of L. sakei CVL-001 according to the experimental schedule alleviated weight loss and disease activity in the mice with colitis. Furthermore, the length and histopathology of the colon improved. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß genes decreased in the colons of mice that were administered L. sakei CVL-001, whereas that of IL-10 increased. The expressions of genes coding for E-cadherin, claudin3, occludin, and mucin were also restored. In co-housed conditions, L. sakei CVL-001 administration did not improve disease activity, colon length, and histopathology. Microbiota analysis revealed that L. sakei CVL-001 administration increased the abundance of microbiota and altered Firmicutes/Bacteroidetes ratio, and decreased Proteobacteria. In conclusion, L. sakei CVL-001 administration protects mice from DSS-induced colitis by regulating immune response and intestinal integrity via gut microbiota modulation.

D-galactose Intake Alleviates Atopic Dermatitis in Mice by Modulating Intestinal Microbiota.

Atopic dermatitis (AD) is one of the most prevalent, chronic and persistent inflammatory skin diseases closely associated with intestinal microbiota. To evaluate the effect of D-galactose intake on AD, we orally administered D-galactose to BALB/c mice whose ears and skin were treated with 2,4-dinitrochlorobenzene (DNCB). D-galactose alleviated DNCB-induced AD-like phenotypes such as redness, scaling/dryness and excoriation. Ear thickness was also decreased by D-galactose administration. Histopathological analysis revealed decreased epidermal thickening, infiltration of immune cells, especially mast cells, in the dermis. Total levels of serum IgE representing the immunological response of AD were decreased by D-galactose administration. Microbiota analysis showed that D-galactose administration restored gut microbiota profiles, which were altered in AD mice, characterized by increased abundance of Bacteroidetes and decreased abundance of Firmicutes. The increased abundance of Bacteroides and the decreased abundance of Prevotella and Ruminococcus were reversed by D-galactose treatment, following improvement of AD. Our results suggest the possible use of D-galactose as a prebiotic to alleviate AD by altering gut microbiota.

The sesquiterpene lactone estafiatin exerts anti-inflammatory effects on macrophages and protects mice from sepsis induced by LPS and cecal ligation puncture.

BACKGROUND: Previously, we found that the water extract of Artermisia scoparia Waldst. & Kit suppressed the cytokine production of lipopolysaccharide (LPS)-stimulated macrophages and alleviated carrageenan-induced acute inflammation in mice. Artemisia contains various sesquiterpene lactones and most of them exert immunomodulatory activity. PURPOSE: In the present study, we investigated the immunomodulatory effect of estafiatin (EST), a sesquiterpene lactone derived from A. scoparia, on LPS-induced inflammation in macrophages and mouse sepsis model. STUDY DESIGN AND METHODS: Murine bone marrow-derived macrophages (BMDMs) and THP-1 cells, a human monocytic leukemia cell line, were pretreated with different doses of EST for 2 h, followed by LPS treatment. The gene and protein expression of pro-inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) were measured by quantitative real-time polymerase chain reaction (qPCR) and Western blot analysis. The activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) was also evaluated at the level of phosphorylation. The effect of EST on inflammatory cytokine production, lung histopathology, and survival rate was assessed in an LPS-induced mice model of septic shock. The effect of EST on the production of cytokines in LPS-stimulated peritoneal macrophages was evaluated by in vitro and ex vivo experiments and protective effect of EST on cecal ligation and puncture (CLP) mice was also assessed. RESULTS: The LPS-induced expression of IL-6, TNF-α, and iNOS was suppressed at the mRNA and protein levels in BMDMs and THP-1 cells, respectively, by pretreatment with EST. The half-maximal inhibitory concentration (IC50) of EST on IL-6 and TNF-α production were determined as 3.2 µM and 3.1 µM in BMDMs, 3 µM and 3.4 µM in THP1 cells, respectively. In addition, pretreatment with EST significantly reduced the LPS-induced phosphorylation p65, p38, JNK, and ERK in both cell types. In the LPS-induced mice model of septic shock, serum levels of IL-6, TNF-α, IL-1ß, CXCL1, and CXCL2 were lower in EST-treated mice than in the control animals. Histopathology analysis revealed that EST treatment ameliorated LPS-induced lung damage. Moreover, while 1 of 7 control mice given lethal dose of LPS survived, 3 of 7 EST-treated (1.25 mg/kg) mice and 5 of 7 EST-treated (2.5 mg/kg) mice were survived. Pretreatment of EST dose-dependently suppressed the LPS-induced production of IL-6, TNF-α and CXCL1 in peritoneal macrophages. In CLP-induced mice sepsis model, while all 6 control mice was dead at 48 h, 1 of 6 EST-treated (1.25 mg/kg) mice and 3 of 6 EST-treated (2.5 mg/kg) mice survived for 96 h. CONCLUSION: These results demonstrated that EST exerts anti-inflammatory effects on LPS-stimulated macrophages and protects mice from sepsis. Our study suggests that EST could be developed as a new therapeutic agent for sepsis and various inflammatory diseases.

Type I Interferons Are Involved in the Intracellular Growth Control of Mycobacterium abscessus by Mediating NOD2-Induced Production of Nitric Oxide in Macrophages.

Mycobacterium abscessus (MAB) is one of the rapidly growing, multidrug-resistant non-tuberculous mycobacteria (NTM) causing various diseases including pulmonary disorder. Although it has been known that type I interferons (IFNs) contribute to host defense against bacterial infections, the role of type I IFNs against MAB infection is still unclear. In the present study, we show that rIFN-ß treatment reduced the intracellular growth of MAB in macrophages. Deficiency of IFN-α/ß receptor (IFNAR) led to the reduction of nitric oxide (NO) production in MAB-infected macrophages. Consistently, rIFN-ß treatment enhanced the expression of iNOS gene and protein, and NO production in response to MAB. We also found that NO is essential for the intracellular growth control of MAB within macrophages in an inhibitor assay using iNOS-deficient cells. In addition, pretreatment of rIFN-ß before MAB infection in mice increased production of NO in the lungs at day 1 after infection and promoted the bacterial clearance at day 5. However, when alveolar macrophages were depleted by treatment of clodronate liposome, rIFN-ß did not promote the bacterial clearance in the lungs. Moreover, we found that a cytosolic receptor nucleotide-binding oligomerization domain 2 (NOD2) is required for MAB-induced TANK binding kinase 1 (TBK1) phosphorylation and IFN-ß gene expression in macrophages. Finally, increase in the bacterial loads caused by reduction of NO levels was reversed by rIFN-ß treatment in the lungs of NOD2-deficient mice. Collectively, our findings suggest that type I IFNs act as an intermediator of NOD2-induced NO production in macrophages and thus contribute to host defense against MAB infection.

Investigation of Mechanical and Hydrologic Characteristics of Porous Asphalt Pavement with a Geocell Composite.

Porous asphalt pavement is a part of the permeable pavement system, which can be used to mitigate the negative impacts of urbanisation on the water hydrological cycle and environment. This study aims to assess the mechanical and hydrologic characteristics of porous asphalt pavements, with and without geocell composites, using a plate load test, falling weight deflectometer test, and rainfall simulation test. The corresponding results indicate that the elastic modulus of the unreinforced pavement is lower than that of the reinforced pavement. The analysis demonstrates that the use of geocell composites effectively increases the load-bearing capacity of the pavement. When the base layer is reinforced with geocells, its load-bearing capacity increases. Observation of the rainfall simulation tests on the reinforced pavement indicates that the reinforced pavement effectively handles the surface runoff.

A Three-Dimensional Microstructure Reconstruction Framework for Permeable Pavement Analysis Based on 3D-IWGAN with Enhanced Gradient Penalty.

Owing to the increasing use of permeable pavement, there is a growing need for studies that can improve its design and durability. One of the most important factors that can reduce the functionality of permeable pavement is the clogging issue. Field experiments for investigating the clogging potential are relatively expensive owing to the high-cost testing equipment and materials. Moreover, a lot of time is required for conducting real physical experiments to obtain physical properties for permeable pavement. In this paper, to overcome these limitations, we propose a three-dimensional microstructure reconstruction framework based on 3D-IDWGAN with an enhanced gradient penalty, which is an image-based computational system for clogging analysis in permeable pavement. Our proposed system first takes a two-dimensional image as an input and extracts latent features from the 2D image. Then, it generates a 3D microstructure image through the generative adversarial network part of our model with the enhanced gradient penalty. For checking the effectiveness of our system, we utilize the reconstructed 3D image combined with the numerical method for pavement microstructure analysis. Our results show improvements in the three-dimensional image generation of the microstructure, compared with other generative adversarial network methods, and the values of physical properties extracted from our model are similar to those obtained via real pavement samples.

Combination of vegetable soup and glucan demonstrates synergistic effects on macrophage-mediated immune responses.

Vegetable soup (VS), a plant-based functional food, has been used as a traditional folk medicine and is attracting attention for its ability to enhance the immune response. ß-Glucan, a well-established and effective immunomodulator, has synergistic effects when used in combination with some bioactive compounds. In the present study, we aimed to evaluate the synergistic immunomodulatory effects of the combination of VS and ß-glucan on macrophage-mediated immune responses. ß-Glucan was demonstrated to synergistically enhance the VS-stimulated immune response, including the production of interleukin-6, tumor necrosis factor-α, and nitric oxide, mainly through the mitogen-activated protein kinase pathway in macrophages. In addition, this combination has the potential for further development in functional foods with immune-enhancing activity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00888-x.

Prediction Models Based on Regression and Artificial Neural Network for Moduli of Layers Constituted by Open-Graded Aggregates.

The impermeable cover in urban area has been growing due to rapid urbanization, which prevents stormwater from being naturally infiltrated into the ground. There is a higher chance of flooding in urban area covered with conventional concretes and asphalts. The permeable pavement is one of Low-Impact Development (LID) technologies that can reduce surface runoff and water pollution by allowing stormwater into pavement systems. Unlike traditional pavements, permeable pavement bases employ open-graded aggregates (OGAs) with highly uniform particle sizes. There is very little information on the engineering properties of compacted OGAs. In this study, the moduli of open-graded aggregates under various compaction energies are investigated based on the Plate Load Test (PLT) and Light-Weight Deflectometer (LWD). Artificial Neural Network (ANN) and Linear Regression (LR) models are employed for estimation of the moduli of the aggregates based on the material type and level of compaction. Overall, the moduli from PLT and LWD steeply increase until the number of roller passes reaches 4, and they gradually increase until the number of roller passes becomes 8. A set of simple linear equations are proposed to evaluate the moduli of open-graded aggregates from PLT and LWD based on the material type and the number of roller passes.

Receptor-interacting protein kinase 2 contributes to host innate immune responses against Fusobacterium nucleatum in macrophages and decidual stromal cells.

PROBLEM: Chorioamnionitis is caused by a bacterial infection that ascends from the vagina and can cause adverse pregnancy outcomes (APOs). Fusobacterium nucleatum (F. nucleatum) is a periodontal pathogen associated with the occurrence of APOs. In this study, we evaluated whether receptor-interacting protein kinase 2 (Ripk2), an adaptor protein of the cytosolic receptors nucleotide-binding oligomerization domain (NOD)1 and NOD2, in macrophages and human decidual stromal cells (hDSCs) contributes to immune responses against F. nucleatum. METHOD OF STUDY: Bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) and Ripk2-deficient mice and hDSCs were cultured with F. nucleatum (MOI 1, 10, 100). BMDMs and hDSCs were assessed using enzyme-linked immunosorbent assay, Western blot analysis, real-time PCR, and nitrite assay. RESULTS: Fusobacterium nucleatum-induced production of IL-6, but not of TNF-α and IL-10, was lower in Ripk2-deficient BMDMs than in WT cells. Western blotting revealed a decrease in F. nucleatum-induced p65 phosphorylation in Ripk2-deficient macrophages, whereas mitogen-activated protein kinases activation was comparable between WT and Ripk2-deficient cells. The production of nitric oxide (NO) in response to F. nucleatum and the gene and protein expression of inducible NO synthase was impaired in Ripk2-deficient BMDMs. In hDSCs, F. nucleatum upregulated the gene and protein expression of NOD1, NOD2, and Ripk2 in a time-dependent manner. F. nucleatum also increased the production of IL-6, CXCL8, and CCL2, whereas this production was decreased by the Ripk2 inhibitors SB203580 and PP2. CONCLUSIONS: In conclusion, Ripk2 signaling appears to contribute to the F. nucleatum-induced immune response and can be a preventive and therapeutic target against APOs.

Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines.

BACKGROUND: Arginine methylation is a posttranslational modification mediated by protein arginine methyltransferases (PRMTs). Although previous studies have shown that PRMT1 contributes to the severity of allergic airway inflammation or asthma, the underlying mechanism is poorly understood. OBJECTIVE: This study aimed to explore the role of PRMT1 and its relevant mechanism in the development of allergic rhinitis (AR). METHODS: The expression levels of PRMTs and cytokines were determined by RT-PCR, and the localization of PRMT1 was determined by immunohistochemistry and confocal microscopy. The levels of house dust mite (HDM)-specific immunoglobulins in serum and of cytokines in nasal lavage fluids were determined by ELISA. PRMT1 inhibition was achieved by siRNA and treatment with the pan PRMT inhibitor arginine N-methyltransferase inhibitor-1. RESULTS: PRMT1 expression was significantly increased in the nasal mucosa of patients and mice with AR. The degree of eosinophilic infiltration in the nasal mucosa was reduced in PRMT1+/- AR mice compared with wild-type mice. PRMT1 haploinsufficiency reduced the levels of HDM-specific immunoglobulins in serum and those of TH2 (IL-4, IL-5, and IL-13) and epithelial (thymic stromal lymphopoietin [TSLP], IL-25, and IL-33) cytokines in the nasal lavage fluids of AR mice. In nasal epithelial cells, HDM and IL-4 cooperate to enhance PRMT1 expression through a mitogen-activated protein kinase-dependent pathway. In addition, PRMT1 was essential for the production of TSLP, IL-25, and IL-33 in response to HDM and IL-4. Arginine N-methyltransferase inhibitor-1 treatment alleviated AR in the mouse model. CONCLUSIONS: PRMT1 plays an important role in AR development by regulating epithelial-derived cytokine production and might be a new therapeutic target for AR.

Water extract of Artemisia scoparia Waldst. & Kitam suppresses LPS-induced cytokine production and NLRP3 inflammasome activation in macrophages and alleviates carrageenan-induced acute inflammation in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia scoparia Waldst. & Kitam (A. scoparia) is a perennial herbal plant that is widely used as a folk remedy in Asian countries. Several studies have demonstrated that A. scoparia has various physiological effects, including anti-inflammation, anti-hypertension, anti-obesity, anti-hepatotoxicity, and anti-oxidant effects. AIM OF THE STUDY: The objective of the present study was to examine the anti-inflammatory effects of water extract of A. scoparia (WAS). MATERIALS AND METHODS: Murine bone marrow-derived macrophages (BMDMs), human monocyte THP-1 and murine fibroblast 3T3-L1 cells were used for the in vitro experiments. Cell viability and cytokine production were determined by the MTT assay and ELISA, respectively. RT-PCR was performed to determine iNOS gene expression and the Griess reaction was used to measure nitrite levels. iNOS protein expression, activation of NF-κB and MAPKs, and cleavage of caspase-1 and IL-1ß were determined by Western blot analysis. A carrageenan-induced mouse model of acute inflammation was used in the in vivo experiments. RESULTS: Pretreatment with WAS concentration-dependently suppressed gene expression and IL-6, TNF-α, CXCL1 and iNOS protein levels in BMDMs stimulated with LPS. In addition, pretreatment with WAS inhibited LPS-induced production of IL-6 and TNF-α in THP-1 cells and CXCL1 in 3T3-L1. Furthermore, LPS induced phosphorylation of p65 in BMDMs, and this induction was dramatically suppressed by WAS pretreatment. We further investigated whether WAS regulates activation of the NLRP3 inflammasome, which is known to be essential for IL-1ß processing. WAS inhibited the production of IL-1ß, but not IL-6, in response to adenosine triphosphate (ATP) and monosodium uric acid (MSU) crystals in LPS-primed BMDMs. Cleavage of caspase-1 and IL-1ß was also reduced by WAS. We finally evaluated the in vivo anti-inflammatory effects of WAS in a mouse model of carrageenan-induced acute inflammation. Subcutaneous administration of WAS reduced production of the inflammatory cytokines IL-6, TNF-α, CXCL1, and IL-1ß. Recruitment of immune cells, mostly neutrophils, was also reduced by administration of WAS. Infiltration of inflammatory cells and edema in the submucosa of air pouch tissues were markedly improved in the WAS-treated groups. CONCLUSIONS: Our results indicate that WAS possesses potent anti-inflammatory properties. These findings suggest that A. scoparia is a candidate functional food targeting several inflammatory diseases.

Cathelicidin-related Antimicrobial Peptide Contributes to Host Immune Responses Against Pulmonary Infection with Acinetobacter baumannii in Mice.

Acinetobacter baumannii is known for its multidrug antibiotic resistance. New approaches to treating drug-resistant bacterial infections are urgently required. Cathelicidin-related antimicrobial peptide (CRAMP) is a murine antimicrobial peptide that exerts diverse immune functions, including both direct bacterial cell killing and immunomodulatory effects. In this study, we sought to identify the role of CRAMP in the host immune response to multidrug-resistant Acinetobacter baumannii. Wild-type (WT) and CRAMP knockout mice were infected intranasally with the bacteria. CRAMP-/- mice exhibited increased bacterial colony-forming units (CFUs) in bronchoalveolar lavage (BAL) fluid after A. baumannii infection compared to WT mice. The loss of CRAMP expression resulted in a significant decrease in the recruitment of immune cells, primarily neutrophils. The levels of IL-6 and CXCL1 were lower, whereas the levels of IL-10 were significantly higher in the BAL fluid of CRAMP-/- mice compared to WT mice 1 day after infection. In an in vitro assay using thioglycollate-induced peritoneal neutrophils, the ability of bacterial phagocytosis and killing was impaired in CRAMP-/- neutrophils compared to the WT cells. CRAMP was also essential for the production of cytokines and chemokines in response to A. baumannii in neutrophils. In addition, the A. baumannii-induced inhibitor of κB-α degradation and phosphorylation of p38 MAPK were impaired in CRAMP-/- neutrophils, whereas ERK and JNK phosphorylation was upregulated. Our results indicate that CRAMP plays an important role in the host defense against pulmonary infection with A. baumannii by promoting the antibacterial activity of neutrophils and regulating the innate immune responses.

Unveiling the Crucial Role of Type IV Secretion System and Motility of Helicobacter pylori in IL-1ß Production via NLRP3 Inflammasome Activation in Neutrophils.

Helicobacter pylori is a gram-negative, microaerophilic, and spiral-shaped bacterium and causes gastrointestinal diseases in human. IL-1ß is a representative cytokine produced in innate immune cells and is considered to be a key factor in the development of gastrointestinal malignancies. However, the mechanism of IL-1ß production by neutrophils during H. pylori infection is still unknown. We designed this study to identify host and bacterial factors involved in regulation of H. pylori-induced IL-1ß production in neutrophils. We found that H. pylori-induced IL-1ß production is abolished in NLRP3-, ASC-, and caspase-1/11-deficient neutrophils, suggesting essential role for NLRP3 inflammasome in IL-1ß response against H. pylori. Host TLR2, but not TLR4 and Nod2, was also required for transcription of NLRP3 and IL-1ß as well as secretion of IL-1ß. H. pylori lacking cagL, a key component of the type IV secretion system (T4SS), induced less IL-1ß production in neutrophils than did its isogenic WT strain, whereas vacA and ureA were dispensable. Moreover, T4SS was involved in caspase-1 activation and IL-1ß maturation in H. pylori-infected neutrophils. We also found that FlaA is essential for H. pylori-mediated IL-1ß production in neutrophils, but not dendritic cells. TLR5 and NLRC4 were not required for H. pylori-induced IL-1ß production in neutrophils. Instead, bacterial motility is essential for the production of IL-1ß in response to H. pylori. In conclusion, our study shows that host TLR2 and NLRP3 inflammasome and bacterial T4SS and motility are essential factors for IL-1ß production by neutrophils in response to H. pylori.

IL-10 Protects Mice From the Lung Infection of Acinetobacter baumannii and Contributes to Bacterial Clearance by Regulating STAT3-Mediated MARCO Expression in Macrophages.

Interleukin-10 plays important, yet contrasting, roles in host protection against bacterial infections and in the septic response. To determine the role of IL-10 in the host defense against Acinetobacter baumannii infection, wild-type (WT) and IL-10-deficient mice were infected intranasally with the bacteria. IL-10-deficient mice exhibited increased mortality, severe pathology, and excess production of proinflammatory cytokines and chemokines in the lungs, and increased bacterial burdens in bronchoalveolar lavage (BAL) fluids and lung homogenates after A. baumannii infection, compared to WT mice. Intranasal administration of recombinant IL-10 rescued mice from the lethality of the bacterial infection by promoting bacterial clearance and reducing production of cytokines and chemokines in the lungs. In vitro experiments revealed that IL-10 enhanced phagocytosis and bacterial killing by macrophages by upregulating the macrophage receptor with collagenous structure (MARCO). In addition, A. baumannii-induced activation of STAT3 was impaired in IL-10-deficient macrophages, which was essential for expression of MARCO. Intranasal adoptive transfer of WT macrophages resulted in significant increases in mice survival and bacterial clearance in IL-10-deficient mice infected with A. baumannii. Our results show that IL-10 played an important role in the host defense against pulmonary infection of A. baumannii by promoting the antibacterial function of macrophages by regulating MARCO expression through the STAT3-mediated pathway.

Dynamic Modulus of Porous Asphalt and the Effect of Moisture Conditioning.

Porous asphalt has been used for permeable pavement to improve safety of roadways and the effectiveness of storm water management. As a surface drainage layer with frequent exposure to water, this material is affected by moisture. In this study, dynamic modulus tests were performed on both moisture unconditioned and conditioned specimens to characterize viscoelastic properties of porous asphalt mixture. The dynamic modulus values of porous asphalt materials with air void content of 9.0% and 20.5% were investigated at dry condition and after specified moisture conditioning cycles. One cycle of moisture conditioning procedure included placing specimens in water tank at 60 °C for 24 h, and then in another water tank at 25 °C for additional 2 h. The results showed that porous asphalt mixture with lower air void content resulted in higher values of dynamic modulus, and these values of porous asphalt with air void content of 9.0% was about 1.5 to 3.0 times that of porous asphalt with air void content of 20.5%. Higher value of the first number of performance graded binder (average 7-day maximum pavement design temperature) seems to make the dynamic modulus values at high temperatures larger. After moisture conditioning, the dynamic modulus of porous asphalt mixture increased, overall, especially at low temperatures. The appropriated selection of asphalt binder, a weakening of asphalt due to moisture damage can be reduced.