Reversal of Long-Term Trends in Ethane Identified from the Global Atmosphere Watch Reactive Gases Measurement Network

Reactive gases play an important role in climate and air pollution issues. They control the self-cleansing capability of the troposphere, contribute to air pollution and acid deposition, regulate the lifetimes and provide tracers for deciphering sources and sinks for greenhouse gases. Within GAW, the focus is placed on long-term, high-quality observations of ozone (O3), carbon monoxide (CO), volatile organic compounds (VOC), nitrogen oxides (NOx), and sulfur dioxide (SO2). More than 100 stations worldwide carry out reactive gases measurements with data reported to two World Data Centers. The reactive gases program in GAW cooperates The WMO GAW Reactive Gases Program with regional networks and other global monitoring initiatives in order to attain a complete picture of the tropospheric chemical composition. Observations are being made by in-situ monitoring, measurements from commercial routine air-crafts (e.g. IAGOS), column observations, and from flask sampling networks. Quality control and coordination of measurements between participating stations are a primary emphasis. GAW reactive gases data in rapid delivery mode are used to evaluate operational atmospheric composition forecasts in the EU Copernicus Atmospheric Monitoring Service. Oversight of the program is provided by GAW-WMO coordinated Reactive Gases Scientific Advisory Committee (RG-SAG)

Suppression of Th17-polarized airway inflammation by rapamycin

Abstract Because Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation. Consecutively, we assessed the efficacy of methylprednisolone, roflumilast, azithromycin, AM80 and rapamycin against acute or chronic Th17-dependent airway inflammation. Quantifiers for Th17-associated inflammation comprised: bronchoalveolar lavage (BAL) differential cell counts, allergen-specific cytokine and immunoglobulin secretion, as well as flow cytometric phenotyping of pulmonary inflammatory cells. Only rapamycin proved effective against acute Th17-dependent airway inflammation, accompanied by increased plasmacytoid dendritic cells (pDCs) and reduced neutrophils as well as reduced CXCL-1 levels in BAL. Chronic Th17-dependent airway inflammation was unaltered by rapamycin treatment. None of the other agents showed efficacy in our models. Our results demonstrate that Th17-dependent airway inflammation is difficult to treat with known agents. However, we identify rapamycin as an agent with inhibitory potential against acute Th17-polarized airway inflammation

Blockade of IL-36 Receptor Signaling Does Not Prevent from TNF-Induced Arthritis

Introduction: Interleukin (IL)-36a is a newly described member of the IL-1 cytokine family with a known inflammatory and pathogenic function in psoriasis. Recently, we could demonstrate that the receptor (IL-36R), its ligand IL-36a and its antagonist IL-36Ra are expressed in synovial tissue of arthritis patients. Furthermore, IL-36a induces MAP-kinase and NFkB signaling in human synovial fibroblasts with subsequent expression and secretion of pro-inflammatory cytokines. Methods: To understand the pathomechanism of IL-36 dependent inflammation, we investigated the biological impact of IL-36a signaling in the hTNFtg mouse. Also the impact on osteoclastogenesis by IL-36a was tested in murine and human osteoclast assays. Results: Diseased mice showed an increased expression of IL-36R and IL-36a in inflamed knee joints compared to wildtype controls. However, preventively treating mice with an IL-36R blocking antibody led to no changes in clinical onset and pattern of disease. Furthermore, blockade of IL-36 signaling did not change histological signs of TNF-induced arthritis. Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays. Conclusion: Thus we conclude that IL-36a does not affect the development of inflammatory arthritis

The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium

Background: Interleukin (IL)-36α is a recently described member of the IL-1 cytokine family with pro-inflammatory and clearly pathogenic properties in psoriasis. Objective: To determine the IL-36α expression in psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA) and osteoarthritis (OA). Methods: Synovial tissues obtained from arthritis patients were stained for IL-36α, IL-36 receptor (IL-36R) and IL-36R antagonist (IL-36Ra) by immunohistochemistry and immunofluorescence. Lysates were examined for IL-36α by western blot analysis. Synovial fibroblasts (FLS) cultured in the presence of IL-36α were assayed for cytokine expression by quantitative real time PCR and multiplex assay. IL-36α-induced signal transduction in FLS was analysed by immunoblotting. Results: Expression of IL-36R and its ligands IL-36α and IL-36Ra was detected in the synovial lining layer and cellular infiltrates of patients with inflammatory arthritis. IL-36α was expressed significantly higher in PsA and RA than in OA synovium. CD138-positive plasma cells were identified as the main cellular source of IL-36α. No differences were observed for the expression of IL-36R and IL-36Ra between PsA, RA and OA. Functionally, IL-36α induced the expression of IL-6 and IL-8 in FLS through p38/NFkB activation. Conclusions: IL-36α is up-regulated in PsA and RA synovium, expressed by tissue plasma cells and leads to IL-6 and IL-8 production by synovial fibroblasts. Hence, IL-36α links plasma cells to inflammatory cytokine production by FLS and may represent a key link between autoimmunity and the induction of synovitis

Reversal of global atmospheric ethane and propane trends largely due to US oil and natural gas production

Non-methane hydrocarbons such as ethane are important precursors to tropospheric ozone and aerosols. Using data from a global surface network and atmospheric column observations we show that the steady decline in ethane concentrations that began in the 1970s halted between 2005 and 2010 in most of the Northern Hemisphere, and has since reversed. We calculate a yearly increase in ethane emissions in the Northern Hemisphere of 0.42 (+/-0.19) Tg/yr between mid-2009 and mid-2014. The largest increases in ethane and for the shorter-lived propane are seen over the central and eastern USA, with a spatial distribution that suggests North American oil and natural gas development as the primary source of increasing emissions. By including other co-emitted oil and natural gas non-methane hydrocarbons, we estimate a Northern Hemisphere total non-methane hydrocarbon yearly emission increase of 1.2 (+/-0.8) Tg/yr. Atmospheric chemical transport modelling suggests that these emissions could augment summertime mean surface ozone by several nanomoles per mole near oil and natural gas production regions. Methane/ethane oil and natural gas emission ratios suggest a significant increase in associated methane emissions; however, this increase is inconsistent with observed leak rates in production regions and changes in methane’s global isotopic ratio

Rsk2 controls synovial fibroblast hyperplasia and the course of arthritis

Objective: Arthritis is a chronic inflammatory disease characterised by immune cell infiltration and mesenchymal cell expansion in the joints. Although the role of immune cells in arthritis is well characterised, the development of mesenchymal cell hyperplasia needs to be better defined. Here, we analysed the role of the ribosomal S6 kinase Rsk2, which we found to be highly activated in joints of patients with arthritis, in the development of mesenchymal cell hyperplasia. Methods: We genetically inactivated Rsk2 in the tumour necrosis factor (TNF)-α transgenic (TNFtg) mice, an animal model for human inflammatory arthritis. Clinical and histological signs of arthritis as well as molecular markers of inflammation and joint destruction were quantified. Fibroblast-like synoviocytes (FLS) were characterised in vitro and the effect of Rsk2 deletion on the pattern of gene expression was determined. Results: Rsk2 deficiency in TNFtg mice results in earlier and exacerbated inflammation as well as increased bone and cartilage destruction. The production of inflammatory cytokines, matrix metalloproteinases and osteoclastogenic molecules was significantly increased in vivo upon Rsk2 inactivation. Bone marrow deficient in Rsk2 could not transfer this phenotype, indicating that Rsk2 expression in mesenchymal cells controls the course of arthritis. Indeed, Rsk2 deficiency was associated with a more activated phenotype and higher proliferative capacity of FLS, thereby increasing cytokines and production of matrix proteinases. Conclusions: Rsk2 emerges as a key regulator of mesenchymal cell numbers in the joint and thereby could be targeted to control the inflammatory and tissue-destructive feature of joints in arthritis

Increased expression of IL36R and IL36α in hTNFtg mice.

<p>otal knee RNA from knee-joints of 6-week-old male wild-type and hTNFtg mice was isolated and quantitative real-time PCR for IL-36 family members was performed. (A) IL36R, (B) IL-36α and (C) IL-36Ra. Relative Expression was calculated from the ratio of the gene of interest to the housekeeping gene β-actin (n = 7–10). Graphs depict mean ±SEM. *p≤0,05, **p≤0,01, ***p≤0,001.</p

Unaltered clinical signs of arthritis in anti-IL36R treated hTNFtg mice.

<p>Clinical parameters: (A) body weight, (B) grip strength, (C) paw thickness and (D) joint thickness were regularly assessed in anti-IL36R treated hTNFtg mice between 4 and 8 weeks of age. Values represent the mean ±SEM (PBS control group n = 8; treatment group n = 9).</p