Although cells of the immune system experience force and pressure throughout their lifecycle, almost nothing is known about how these mechanical processes regulate the immune response 1. Both tissue-resident and tissue-infiltrating immune cells in highly mechanical organs, such as the lung, are constantly exposed to tonic and dynamically changing mechanical cues 2. Here using reverse genetics, we show that myeloid cells respond to force and alterations in cyclical hydrostatic pressure via the mechanosensory ion channel PIEZO1 3. Unbiased RNA sequencing from macrophages subjected to cyclical hydrostatic pressure reveals a striking state of proinflammatory reprogramming. We report a novel mechanosensory-immune signaling circuit which PIEZO1 initiates in response to cyclical hydrostatic pressure, driving c-JUN activation and transcriptional upregulation of Endothelin-1 (EDN1). EDN1 in turn stabilizes HIF1α, which facilitates transcription of a potent and prolonged program of proinflammatory mediators. Using mice conditionally deficient of PIEZO1 in myeloid cells, and cellular depletion assays, we show 10

No abstract

Lung fibrosis is the hallmark of the interstitial lung diseases. Alveolar epithelial cell (AEC) injury is akey step that contributes to a profibrotic microenvironment. Fibroblasts and myofibroblasts subsequently accumulate and deposit excessive extracellular matrix. In addition to TGF‐β, the IL‐6 family of cytokines, which signal through STAT‐3, may also contribute to lung fibrosis. In the current manuscript, the extent to which STAT‐3 inhibition decreases lung fibrosis is investigated. Phosphorylated STAT‐3 was elevated in lung biopsies from patients with idiopathic pulmonary fibrosis and bleomycin (BLM)‐induced fibrotic murine lungs. C‐188‐9, a small molecule STAT‐3 inhibitor, decreased pulmonary fibrosis in the intraperitoneal BLM model as assessed by arterial oxygen saturation (control, 84.4 ± 1.3%; C‐188‐9, 94.4 ± 0.8%), histology (Ashcroft score: untreated, 5.4 ± 0.25; C‐188‐9, 3.3 ± 0.14), and attenuated fibrotic markers such as diminished α‐smooth muscle actin, reduced collagen deposition. In addition, C‐188‐9 decreased the expression of epithelial injury markers, including hypoxia‐inducible factor‐1α (HIF‐1α) and plasminogen activator inhibitor‐1 (PAI‐1). In vitro studies show that inhibition of STAT‐3 decreased IL‐6‐ and TGF‐β‐induced expression of multiple genes, including HIF‐1α and PAI‐1, in AECs. Furthermore, C‐188‐9 decreased fibroblast‐to‐myofibroblast differentiation. Finally, TGF‐β stimulation of lung fibroblasts resulted in SMAD2/SMAD3‐dependent phosphorylation of STAT‐3. These findings demonstrate that STAT‐3 contributes to the development of lung fibrosis and suggest that STAT‐3 may be a therapeutic target in pulmonary fibrosis.—Pedroza, M., Le, T. T., Lewis, K., Karmouty‐Quintana, H., To, S., George, A. T., Blackburn, M. R., Tweardy, D. J., Agarwal, S. K. STAT‐3 contributes to pulmonary fibrosis through epithelial injury and fibroblast‐myofibroblast differentiation. FASEB J. 30, 129‐140 (2016). http://www.fasebj.org

A glut of inexpensive glycerol has resulted from expanding biodiesel production around the world. This glycerol could be used as a good renewable source to produce hydrogen fuel. Hydrogen production from glycerol via a steam reforming process over Ni/CeO2, Ni/MgO, and Ni/TiO2 catalysts was studied. The catalysts were characterized by using X-ray diffraction, thermogravimetric analysis, BET surface area analysis, metal dispersion, active surface area analysis, and hydrogen temperature programmed reduction. Ni/CeO2 had the highest surface area (67.0 m2/g) followed by Ni/TiO2 (64.9 m2/g) and Ni/MgO (50.2 m2/g). Also, Ni/CeO2 showed the highest metal dispersion (6.14%) compared to Ni/MgO (0.38%) and Ni/TiO2 (0.29%). Effects of reaction temperatures, feed flow rates (FFRs), and water/glycerol molar ratios (WGMRs) on hydrogen selectivity and glycerol conversion were analyzed. Ni/CeO2 was found to be the best performing catalyst compared to Ni/MgO and Ni/TiO2 under the experimental conditions investigated. Ni/CeO2 gave the maximum hydrogen selectivity of 74.7% at a WGMR of 12:1, temperature of 600 °C, and FFR of 0.5 mL/min compared to Ni/MgO (38.6%) and Ni/TiO2 (28.3%) under similar conditions.

No abstract