Pattern recognition receptors detect microbial products and induce cytokines, which shape the immunological response. IL-12, TNF-α, and IL-1β are proinflammatory cytokines, which are essential for resistance against infection, but when produced at high levels they may contribute to immunopathology. In contrast, IL-10 is an immunosuppressive cytokine, which dampens proinflammatory responses, but it can also lead to defective pathogen clearance. The regulation of these cytokines is therefore central to the generation of an effective but balanced immune response. In this study, we show that macrophages derived from C57BL/6 mice produce low levels of IL-12, TNF-α, and IL-1β, but high levels of IL-10, in response to TLR4 and TLR2 ligands LPS and Pam3CSK4, as well as Burkholderia pseudomallei, a Gram-negative bacterium that activates TLR2/4. In contrast, macrophages derived from BALB/c mice show a reciprocal pattern of cytokine production. Differential production of IL-10 in B. pseudomallei and LPS-stimulated C57BL/6 and BALB/c macrophages was due to a type I IFN and ERK1/2-dependent, but IL-27–independent, mechanism. Enhanced type I IFN expression in LPS-stimulated C57BL/6 macrophages was accompanied by increased STAT1 and IFN regulatory factor 3 activation. Furthermore, type I IFN contributed to differential IL-1β and IL-12 production in B. pseudomallei and LPS-stimulated C57BL/6 and BALB/c macrophages via both IL-10–dependent and –independent mechanisms. These findings highlight key pathways responsible for the regulation of pro- and anti-inflammatory cytokines in macrophages and reveal how they may differ according to the genetic background of the host.
The aim of this study was to investigate the protective effects of matrine on lipopolysaccharide (LPS)-induced inflammation and oxidative stress in vivo and in vitro. The results showed that matrine improved intestinal inflammatory status and oxidative balance and enhanced chemokine receptor 7 (CCR7) expression. In LPS-challenged mice and Caco-2 cells, matrine alleviated LPS-induced inflammation and oxidative stress via downregulating pro-inflammatory cytokines (IL-1β and IL-17) and malondialdehyde (MDA) production. CCR7-siRNA transfection blocked the protective effects of matrine on LPS-induced inflammation and oxidative stress and exacerbated LPS caused injury. In conclusion, matrine alleviates LPS-induced intestinal inflammation and oxidative stress in mice and Caco-2 cells, which may be associated with CCR7 signal.
works on integrative approaches to solve environmental problems. He holds a bachelor's degree in anthropology and a master of science in environmental sustainability. He is currently a PhD candidate developing new approaches towards collaborative design of agricultural development innovations. His current research focus is on Xishuangbanna using participatory and descriptive research methods to better understand the context in which innovations may be adopted; and also in Guatemala using a similar set of methods to approach a different set of problems.Zhuangfang Yi is a member of the Xishuangbanna ethnic minority. She obtained her PhD studying marketbased incentive schemes for the promotion of eco-friendly rubber in Xishuangbanna. As a research fellow at ICRAF, Dr Yi has published several peer-reviewed journal articles, reports and a book chapter in varying Leadership Group, she has also helped the Xishuangbanna government to develop their 12th 5-year biodiversity
Timothy McLellanTim holds a bachelor's degree in law and Chinese from The School of Oriental and African Studies, a master's degree in law and anthropology from the London School of Economics, and is currently a PhD candidate in anthropology at Cornell University. As a member of ICRAF East and Central Asia's soil biology group, Tim is conducting research into mushroom harvesting and forest resource use across Northern Thailand, and Yunnan, including in Xishuangbanna.Jiawen Zhao bachelor's degree in Global Business Management from the University of Macau. She will continue her master degree in Manufacturing Management at the University of Windsor, Canada. As a member of the Humidtropics team, Ms Zhao is responsible for the communication and interpretation between researchers and the locals, as well as logistics.
Antibiotics are widely found in nitrogen-containing
wastewater,
which may affect the operation stability of anaerobic ammonium oxidation
(anammox)-based biological treatment systems. Extracellular polymeric
substances (EPSs) of anammox sludge play a pivotal role in combining
with antibiotics; however, the exact role and how the structure of
the leading component of EPSs (i.e., extracellular proteins) changes
under antibiotic stress remain to be elucidated. Here, the interaction
between sulfamethoxazole and the extracellular proteins of anammox
sludge was investigated via multiple spectra and molecular simulation.
Results showed that sulfamethoxazole statically quenched the fluorescent
components of EPSs, and the quenching constant of the aromatic proteins
was the largest, with a value of 1.73 × 104 M–1. The overall binding was an enthalpy-driven process,
with ΔH = −75.15 kJ mol–1, ΔS = −0.175 kJ mol–1 K–1, and ΔG = −21.10
kJ mol–1 at 35 °C. The O-P-O and CO
groups responded first under the disturbance of sulfamethoxazole.
Excessive sulfamethoxazole (20 mg L–1) would decrease
the ratio of α-helix/(β-sheet + random coil) of extracellular
proteins, resulting in a loose structure. Molecular docking and dynamic
simulation revealed that extracellular proteins would provide abundant
sites to bind with sulfamethoxazole, through hydrogen bond and Pi-Akyl
hydrophobic interaction forces. Once sulfamethoxazole penetrates into
the cell surface and combines with the transmembrane ammonium transport
domain, it may inhibit the NH4
+ transport. Our
findings enhance the understanding on the interaction of extracellular
proteins and sulfamethoxazole, which may be valuable for deciphering
the response property of anammox sludge under the antibiotic stress.
Strong metal–support interaction (SMSI) over Ru/CaAlOx was constructed by utilizing the surface structural reconstruction of Ca–Al layered double hydroxides (LDHs) in aqueous solution and their subsequent hydroxide-to-oxide transformations.
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