Differential effects of cytokines and corticosteroids on Toll-like receptor 2 expression and activity in human airway epithelia

<p>Abstract</p> <p>Background</p> <p>The recognition of microbial molecular patterns via Toll-like receptors (TLRs) is critical for mucosal defenses.</p> <p>Methods</p> <p>Using well-differentiated primary cultures of human airway epithelia, we investigated the effects of exposure of the cells to cytokines (TNF-α and IFN-γ) and dexamethasone (dex) on responsiveness to the TLR2/TLR1 ligand Pam3CSK4. Production of IL-8, CCL20, and airway surface liquid antimicrobial activity were used as endpoints.</p> <p>Results</p> <p>Microarray expression profiling in human airway epithelia revealed that first response cytokines markedly induced TLR2 expression. Real-time PCR confirmed that cytokines (TNF-α and IFN-γ), dexamethasone (dex), or cytokines + dex increased TLR2 mRNA abundance. A synergistic increase was seen with cytokines + dex. To assess TLR2 function, epithelia pre-treated with cytokines ± dex were exposed to the TLR2/TLR1 ligand Pam3CSK4 for 24 hours. While cells pre-treated with cytokines alone exhibited significantly enhanced IL-8 and CCL20 secretion following Pam3CSK4, mean IL-8 and CCL20 release decreased in Pam3CSK4 stimulated cells following cytokines + dex pre-treatment. This marked increase in inflammatory gene expression seen after treatment with cytokines followed by the TLR2 ligand did not correlate well with NF-κB, Stat1, or p38 MAP kinase pathway activation. Cytokines also enhanced TLR2 agonist-induced beta-defensin 2 mRNA expression and increased the antimicrobial activity of airway surface liquid. Dex blocked these effects.</p> <p>Conclusion</p> <p>While dex treatment enhanced TLR2 expression, co-administration of dex with cytokines inhibited airway epithelial cell responsiveness to TLR2/TLR1 ligand over cytokines alone. Enhanced functional TLR2 expression following exposure to TNF-α and IFN-γ may serve as a dynamic means to amplify epithelial innate immune responses during infectious or inflammatory pulmonary diseases.</p

Centrality dependent particle production at y=0 and y similar to 1 in Au+Au collisions at root s(NN)=200 GeV

52 authors, 8 pages, 12 Figures, 3 Tables, submitted to PRCParticle production of identified charged hadrons, $\pi^{\pm}$, $K^{\pm}$, $p$, and $\bar{p}$ in Au+Au collisions at $\sqrt(snn) =$ 200 GeV has been studied as a function of transverse momentum and collision centrality at $y=0$ and $y\sim1$ by the BRAHMS experiment at RHIC. Significant collective transverse flow at kinetic freeze-out has been observed in the collisions. The magnitude of the flow rises with the collision centrality. Proton and kaon yields relative to the pion production increase strongly as the transverse momentum increases and also increase with centrality. Particle yields per participant nucleon show a weak dependence on the centrality for all particle species. Hadron production remains relatively constant within one unit around midrapidity in Au+Au collisions at $\sqrt(snn) =$ 200 GeV

A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis.

OBJECTIVE: To evaluate treatment with methotrexate (MTX) in patients with newly diagnosed giant cell arteritis (GCA) to determine if MTX reduces GCA relapses and cumulative corticosteroid (CS) requirements and diminishes disease- and treatment-related morbidity. METHODS: This was a multicenter, randomized, double-blind study. Over 4 years, 16 centers from the International Network for the Study of Systemic Vasculitides enrolled patients with unequivocal GCA. The initial treatment was 1 mg/kg/day

Forward and midrapidity like-particle ratios from p+p collisions at root s=200 GeV

We present a measurement of π−/π+π−/π+, K−/K+K−/K+ and p¯/p from p+pp+p collisions at s=200 GeV over the rapidity range 02.0y>2.0. The p¯/p ratio is very similar for p+pp+p and 20% central Au + Au collisions at all rapidities. In the fragmentation region the three ratios seem to be independent of beam energy when viewed from the rest frame of one of the protons. Theoretical models based on quark–diquark breaking mechanisms overestimate the p¯/p ratio up to y≲3y≲3. Including additional mechanisms for baryon number transport such as baryon junctions leads to a better description of the data