IL-4–Stat6 Signaling Induces Tristetraprolin Expression and Inhibits TNF-α Production in Mast Cells

Increasing evidence has revealed that mast cell–derived tumor necrosis factor α (TNF-α) plays a critical role in a number of inflammatory responses by recruiting inflammatory leukocytes. In this paper, we investigated the regulatory role of interleukin 4 (IL-4) in TNF-α production in mast cells. IL-4 inhibited immunoglobulin E–induced TNF-α production and neutrophil recruitment in the peritoneal cavity in wild-type mice but not in signal transducers and activators of transcription 6 (Stat6)–deficient mice. IL-4 also inhibited TNF-α production in cultured mast cells by a Stat6-dependent mechanism. IL-4–Stat6 signaling induced TNF-α mRNA destabilization in an AU-rich element (ARE)–dependent manner, but did not affect TNF-α promoter activity. Furthermore, IL-4 induced the expression of tristetraprolin (TTP), an RNA-binding protein that promotes decay of ARE-containing mRNA, in mast cells by a Stat6-dependent mechanism, and the depletion of TTP expression by RNA interference prevented IL-4–induced down-regulation of TNF-α production in mast cells. These results suggest that IL-4–Stat6 signaling induces TTP expression and, thus, destabilizes TNF-α mRNA in an ARE-dependent manner

Effects of Green Tea Catechins and Theanine on Preventing Influenza Infection among Healthcare Workers: A Randomized Controlled Trial

<p>Abstract</p> <p>Background</p> <p>Experimental studies have revealed that green tea catechins and theanine prevent influenza infection, while the clinical evidence has been inconclusive. This study was conducted to determine whether taking green tea catechins and theanine can clinically prevent influenza infection.</p> <p>Methods</p> <p><b>Design, Setting, and Participants</b>: A randomized, double-blind, placebo-controlled trial of 200 healthcare workers conducted for 5 months from November 9, 2009 to April 8, 2010 in three healthcare facilities for the elderly in Higashimurayama, Japan.</p> <p><b>Interventions</b>: The catechin/theanine group received capsules including green tea catechins (378 mg/day) and theanine (210 mg/day). The control group received placebo.</p> <p><b>Main Outcome Measures</b>: The primary outcome was the incidence of clinically defined influenza infection. Secondary outcomes were (1) laboratory-confirmed influenza with viral antigen measured by immunochromatographic assay and (2) the time for which the patient was free from clinically defined influenza infection, i.e., the period between the start of intervention and the first diagnosis of influenza infection, based on clinically defined influenza infection.</p> <p>Results</p> <p>Eligible healthcare workers (n = 197) were enrolled and randomly assigned to an intervention; 98 were allocated to receive catechin/theanine capsules and 99 to placebo. The incidence of clinically defined influenza infection was significantly lower in the catechin/theanine group (4 participants; 4.1%) compared with the placebo group (13 participants; 13.1%) (adjusted OR, 0.25; 95% CI, 0.07 to 0.76, <it>P </it>= 0.022). The incidence of laboratory-confirmed influenza infection was also lower in the catechin/theanine group (1 participant; 1.0%) than in the placebo group (5 participants; 5.1%), but this difference was not significant (adjusted OR, 0.17; 95% CI, 0.01 to 1.10; <it>P </it>= 0.112). The time for which the patient was free from clinically defined influenza infection was significantly different between the two groups (adjusted HR, 0.27; 95% CI, 0.09 to 0.84; <it>P </it>= 0.023).</p> <p>Conclusions</p> <p>Among healthcare workers for the elderly, taking green tea catechins and theanine may be effective prophylaxis for influenza infection.</p> <p>Trial Registration</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT01008020">NCT01008020</a></p