Blood

Senechal and coworkers   investigated whether diesel exhausts favor Th2-associated allergic reactions either by increasing production of Th2-associated chemokines and their associated receptors or by decreasing Th1-attracting chemokines and chemokine receptors. Exposure of peripheral blood mononuclear cells from patients with asthma to diesel induced release of I-309; this effect did not occur with allergen exposure. Both diesel and Defr p 1 induced early but transient release of monokine induced by interferon- and late release of pulmonary and activation-regulated chemokine. Both Th1- and Th2-attracting chemokines were induced, but the resulting effect was increased chemotactic activity of Th2 cells and not of Th1 cells. Diesel induced a late increase in the expression of the Th1-associated CXC receptor 3 and CC receptor 5. Upregulation of T cell CXC receptor 3 was not associated with increased migration to its ligands. The authors conclude that diesel, even in the absence of allergen, amplifies Th2 immune response and that it also increases late Th1-associated chemoreceptor expression.

The transcription factor, nuclear factor-B, is inactive when it is bound to its inhibitory protein, IB. When a cell is stimulated by inflammatory signals, IB is phosphorylated by IB kinases and degraded, and the released nuclear factor-B induces expression of cytokines, such as granulocyte-macrophage colony–stimulating factor, interleukin-8, and regulated upon activation, normal T cell expressed and secreted (RANTES). In patients with asthma, Gagliardo and coworkers   found that an inhibitor of nuclear factor-B activation, pyrrolidinedithiocarbamate, markedly decreased these mediators. Three groups of patients with asthma (6 with mild controlled; 8 with moderate uncontrolled; and 20 with severe uncontrolled) exhibited large amount of phosphorylated IB. Compared with healthy subjects, patients with moderate or severe asthma had higher levels of IB kinase ß and p65 in peripheral blood mononuclear cells. The activation status of p65 was greater in patients with severe asthma. The authors conclude that peripheral blood mononuclear cells of patients with severe uncontrolled asthma exhibit increased levels of p65, phosphorylated IB, and IB kinases, and that exaggerated activation of nuclear factor-B perpetuates the production of inflammatory mediators in asthma.

Citations 1-3 of 3 total displayed.

Decreased Arginine Bioavailability and Increased Serum Arginase Activity in Asthma

Claudia R. Morris, Mirjana Poljakovic, Lisa Lavrisha, Lorenzo Machado, Frans A. Kuypers, and Sidney M. Morris, Jr.
Am. J. Respir. Crit. Care Med. 170: 148 -153. First published online as doi:10.1164/rccm.200309-1304OC [Abstract] [Full text]  

Persistent Activation of Nuclear Factor–B Signaling Pathway in Severe Uncontrolled Asthma

Rosalia Gagliardo, Pascal Chanez, Marc Mathieu, Andreina Bruno, Giorgia Costanzo, Claire Gougat, Isabelle Vachier, Jean Bousquet, Giovanni Bonsignore, and Antonio M. Vignola
Am. J. Respir. Crit. Care Med. 168: 1190 -1198. First published online as doi:10.1164/rccm.200205-479OC [Abstract] [Full text]  

Effect of Diesel on Chemokines and Chemokine Receptors Involved in Helper T Cell Type 1/Type 2 Recruitment in Patients with Asthma

Stéphanie Sénéchal, Patricia de Nadai, Natacha Ralainirina, Arnaud Scherpereel, Han Vorng, Philippe Lassalle, André-Bernard Tonnel, Anne Tsicopoulos, and Benoît Wallaert
Am. J. Respir. Crit. Care Med. 168: 215 -221. First published online as doi:10.1164/rccm.200211-1289OC [Abstract] [Full text]