Pseudomonas aeruginosa Induces Interferon-β Production to Promote Intracellular Survival.

Pseudomonas aeruginosa (PA) is known as one kind of extracellular pathogens. However, more evidence showed that PA encounters the intracellular environment in different mammalian cell types. Little is known of innate immune factors modulating intracellular PA survival.

Airway acidification impaired host defense against infection by promoting type 1 interferon β response.

Airway microenvironment played an important role in the progression of chronic respiratory disease. Here we showed that standardized pondus hydrogenii (pH) of exhaled breath condensate (EBC) of bronchiectasis patients was significantly lower than that of controls and was significantly correlated with bronchiectasis severity index (BSI) scores and disease prognosis. EBC pH was lower in severe patients than that in mild and moderate patients.

Albumin-Based LL37 Peptide Nanoparticles as a Sustained Release System against Lung Infection.

(PA) has emerged as a pressing challenge to pulmonary infection and lung damage. The LL37 peptide is an efficient antimicrobial agent against PA strains, but its application is limited because of fast clearance , biosafety concerns, and low bioavailability. Thus, an albumin-based nanodrug delivery system with reduction sensitivity was developed by forming intermolecular disulfide bonds to increase LL37 performance against PA.

Corticosteroids alleviate lipopolysaccharide-induced inflammation and lung injury via inhibiting NLRP3-inflammasome activation.

The role of corticosteroids in acute lung injury (ALI) remains uncertain. This study aims to determine the underlying mechanisms of corticosteroid treatment for lipopolysaccharide (LPS)-induced inflammation and ALI. We used corticosteroid treatment for LPS-induced murine ALI model to investigate the effect of corticosteroid on ALI in vivo.

PM2.5 compromises antiviral immunity in influenza infection by inhibiting activation of NLRP3 inflammasome and expression of interferon-β.

PM2.5, a major component of air pollutants, has caused severe health problems. It has been reported that PM2.

Macrolides protect against infection via inhibition of inflammasomes.

Macrolides antibiotics have been effectively used in many chronic diseases, especially with infection. The mechanisms underlying the therapeutic effects of macrolides in these diseases remain poorly understood. We established a mouse model of chronic lung infection using agar-beads, with azithromycin treatment or placebo.

Porphyromonas gingivalis infected macrophages upregulate CD36 expression via ERK/NF-κB pathway.

CD36, a scavenger receptor, plays an important role in the progression of atherosclerosis through its interaction with oxidized low-density lipoprotein (ox-LDL). Porphyromonas gingivalis (P. gingivalis, Pg) has been shown to promote macrophage-derived foam cell formation by affecting the expression of CD36.

IL-10 negatively regulates oxLDL-P38 pathway inhibited macrophage emigration.

The effect of IL-10 on macrophage migration was investigated, including the analysis of protein expression, cytokine secretion and activation of the MAPKs and NF-kB pathway. The expression of endogenic IL-10 was down-regulated in macrophage stimulated with oxLDL for indicated time. Exogenous IL-10 reversed oxLDL-inhibited chemotactic macrophage numbers by 48.

Nuclear hormone receptor regulation of microRNAs controls innate immune responses in C. elegans.

Nuclear hormone receptors respond to small molecules such as retinoids or steroids and regulate development. Signaling in the conserved p38/PMK-1 MAP kinase pathway regulates innate immunity. In this study, we show that the Caenorhabditis elegans nuclear receptor DAF-12 negatively regulates the defense against pathogens via the downstream let-7 family of microRNAs, which directly target SKN-1, a gene downstream of PMK-1.

An essential function for MKP5 in the formation of oxidized low density lipid-induced foam cells.

The uptake of oxidized low density lipoprotein (ox-LDL) by macrophages usually leads to the formation of lipid-laden macrophages known as "foam cells," and this process plays an important role in the development of atherosclerosis. Ox-LDL activates mitogen-activated protein kinase (MAP) kinases and nuclear factor (NF)-κB, and activations of p38 and NF-κB are important for the formation of foam cells. MAP kinase phosphatase (MKP) 5 is a member of the dual specificity phosphatases (DUSPs) family that can selectively dephosphorylate activated MAPKs to regulate innate and adaptive immune responses.

Effects of preconditioning with sevoflurane on TNF-α-induced permeability and activation of p38 MAPK in rat pulmonary microvascular endothelial cells.

Preconditioning with sevoflurane (SPC) diminishes effusion of rat alveolar membrane during inflammation. It is not clear whether this preconditioning directly inhibits permeability of pulmonary microvascular endothelial cell (PMVEC) monolayer. In this article, we evaluated effects of SPC on permeability of PMVEC monolayer and identified signaling pathways involved in these effects.

A broadly flavivirus cross-neutralizing monoclonal antibody that recognizes a novel epitope within the fusion loop of E protein.

Flaviviruses are a group of human pathogenic, enveloped RNA viruses that includes dengue (DENV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses. Cross-reactive antibodies against Flavivirus have been described, but most of them are generally weakly neutralizing. In this study, a novel monoclonal antibody, designated mAb 2A10G6, was determined to have broad cross-reactivity with DENV 1-4, YFV, WNV, JEV, and TBEV.

Association of supervillin with KIR2DL1 regulates the inhibitory signaling of natural killer cells.

Inhibitory signaling is crucial in the regulation of the cytotoxicity of natural killer (NK) cells. Here, we show that KIR2DL1, an inhibitory receptor of NK cells, associates with supervillin, an F-actin binding protein. Interaction of supervillin with KIR2DL1 is dependent on the KIR2DL1 receptor stimulation and requires the phosphorylation of tyrosines in both ITIM motifs.

MicroRNA-101 targets MAPK phosphatase-1 to regulate the activation of MAPKs in macrophages.

MAPK phosphatase-1 (MKP-1) is an archetypical member of the dual-specificity phosphatase family that deactivates MAPKs. Induction of MKP-1 has been implicated in attenuating the LPS- or peptidoglycan-induced biosynthesis of proinflammatory cytokines, but the role of noncoding RNA in the expression of the MKP-1 is still poorly understood. In this study, we show that MKP-1 is a direct target of microRNA-101 (miR-101).

[Effects of isoflurane, sevoflurane and desflurane on expression of ICAM-1 and VCAM-1 in LPS-induced rat lung microvascular endothelial cells].

Objective: To investigate the effect of isoflurane, sevoflurane and desflurane on the expression of ICAM-1 and VCAM-1 in LPS-induced rat lung microvascular endothelial cells (RLMVECs).

Methods: Cultured LPS-treated RLMVECs were exposed to 0.7, 1.

An essential role for RIG-I in toll-like receptor-stimulated phagocytosis.

Retinoic acid-inducible gene-I (RIG-I) plays an important role in antiviral response by recognizing double-stranded RNA. Here we demonstrate an unanticipated role of RIG-I in Toll-like receptor (TLR)-stimulated phagocytosis. Stimulation with lipopolysaccharide (LPS), a ligand of TLR4, induced the expression of RIG-I in macrophages.

JNK regulates cell migration through promotion of tyrosine phosphorylation of paxillin.

The adaptor protein paxillin plays an important role in cell migration. Although the c-Jun amino-terminal kinase (JNK) phosphorylation of paxillin on Ser 178 has been found to be critical for cell migration, the precise mechanism by which JNK regulates cell migration is still not very clear. Here, the migration of human corneal epithelial (HCE) cells was used to determine which signaling pathways are involved in EGF-induced paxillin phosphorylation.

RIG-I plays a critical role in negatively regulating granulocytic proliferation.

RIG-I has been implicated in innate immunity by sensing intracellular viral RNAs and inducing type I IFN production. However, we have found a significant RIG-I induction in a biological setting without active viral infection-namely, during RA-induced terminal granulocytic differentiation of acute myeloid leukemias. Here, we present evidence that a significant Rig-I induction also occurs during normal myelopoiesis and that the disruption of the Rig-I gene in mice leads to the development of a progressive myeloproliferative disorder.

An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells.

The inhibitory signaling of natural killer (NK) cells is crucial in the regulation of innate immune responses. Here we show that the association of KIR2DL1, an inhibitory receptor of NK cells, with beta-arrestin 2 mediated recruitment of the tyrosine phosphatases SHP-1 and SHP-2 to KIR2DL1 and facilitated 'downstream' inhibitory signaling. Consequently, the cytotoxicity of NK cells was higher in beta-arrestin 2-deficient mice but was inhibited in beta-arrestin 2-transgenic mice.

MyD88-independent activation of a novel actin-Cdc42/Rac pathway is required for Toll-like receptor-stimulated phagocytosis.

Phagocytosis and subsequent degradation of pathogens by macrophages play a pivotal role in host innate immune responses to microbial infection. Recent studies have shown that Toll-like receptors (TLRs) play an important role in promoting the clearance of bacteria by up-regulating the phagocytic activity of macrophages. However, information regarding the signaling mechanism of TLR-mediated phagocytosis is still limited.

Andrograpanin, isolated from Andrographis paniculata, exhibits anti-inflammatory property in lipopolysaccharide-induced macrophage cells through down-regulating the p38 MAPKs signaling pathways.

Andrographis paniculata Nees is an official herbal medicine for treatment of infection and inflammation in China. Andrograpanin, the one of diterpene lactones in A. paniculata, is a hydrolysate from neoandrographolide in vivo and in vitro.

Molecular identification and functional characterization of a Drosophila dual-specificity phosphatase DMKP-4 which is involved in PGN-induced activation of the JNK pathway.

MAP (Mitogen-activated protein) kinases play an important role in regulating many critical cellular processes. The inactivation of MAP kinases is always accomplished by a family of dual-specificity phosphatases, termed MAPK phosphatases (MKPs). Here, we have identified a novel MKP-like protein, designated DMKP-4, from the Drosophila genome.

Inhibitory effects of neoandrographolide on nitric oxide and prostaglandin E2 production in LPS-stimulated murine macrophage.

Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), produce excessive amounts of nitric oxide (NO) and prostaglandin E(2) (PGE(2)), which play key roles in the processes of inflammation. Andrographis paniculata Nees is a traditional Chinese herb commonly used for treatment of infection, inflammation, and diarrhea. However, the mechanism of its therapeutic function is not well known.

Feedback control of MKP-1 expression by p38.

Mitogen-activated protein (MAP) kinases play a critical role in innate immune responses to microbial infection through eliciting the biosynthesis of proinflammatory cytokines. MAP phosphatases (MKP)-1 is an archetypical member of the dual-specificity phosphatase family that deactivates MAP kinases. Induction of MKP-1 has been implicated in attenuating the lipopolysaccharide (LPS) and Peptidoglycan (PGN) responses, but how the expression of the MKP-1 is regulated is still not fully understood.

Andrographolide inhibits the production of TNF-alpha and interleukin-12 in lipopolysaccharide-stimulated macrophages: role of mitogen-activated protein kinases.

Andrographolide has been reported to possess a variety of pharmacological activities. In this study, we have investigated the effect of andrographolide on the production of TNF-alpha and IL-12 (Interleukin-12) in murine peritoneal macrophages. Andrographolide decreased TNF-alpha, IL-12a and IL-12b at mRNA level, and reduced the production of TNF-alpha and IL-12p70 proteins in a concentration-dependent manner.