Transcription in response to physical stress—clues to the molecular mechanisms of exercise‐induced asthma

Abstract

To clarify stress-induced immunological reactions and molecular events during exercise and the potential relevance to exercise-induced bronchoconstriction, transcriptional responses to standardized physical stress were determined. Six healthy, young volunteers underwent an endurance exercise of 90% of their individual anaerobic threshold for 90 min. Time-dependent alterations in the expression pattern of leukocytes from healthy, trained subjects were analyzed by DNA microarrays before and 2 h and 6 h after exercise. Starting out from a large collection of cDNA library clones comprising more than 70,000 human expressed sequence tags, we selected, designed, and immobilized oligonucleotide probes (60-70mers) for transcripts of 5000 stress- and inflammation-relevant genes. Exercise-induced stress provoked changes in the expression of 433 gene activities 2 h and/or 6 h after exercise, which could be grouped into six clusters. The most prominent feature was an enhanced transcription of two genes, coding for 5-lipoxygenase (ALOX5) and ALOX5-activating protein. Moreover, enhanced levels of leukotriene B4 (LTB4) and LTC4 (P<0.05) were detected in plasma after exercise. Our data demonstrate that exercise alters the activities of a distinct number of genes. In particular, they possibly provide novel insights into the molecular mechanisms of exercise-induced bronchoconstriction and suggest that enhanced transcription of ALOX5 and its activating protein together with a present predisposition of the subject critically contribute to exercise-induced asthma.

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

“…Numerous potential nonmuscle sources of lipid mediators also exist, however, including neutrophils (PGs and LTs), platelets (TXB 2 and 12-HETE), monocytes/macrophages (15-HETE), vascular endothelial cells (PGI 2 ), and transcellular interactions (lipoxins and resolvins). Previous reports of elevated postexercise leukocyte COX-2 and 5-LOX expression (40,47), COX-2 mRNA expression within human postexercise muscle biopsies (60,109), and 5-LOX expression within resting skeletal muscle tissue (111) suggests that leukocytes and exercised skeletal muscle tissue itself are potential sites of elevated LT and PG biosynthesis. Whether skeletal muscle can participate in the biosynthesis of other lipid mediator species measured, including proresolving mediators, either directly, or via transcellular cross talk with locally accumulating inflammatory cells is not known.…”

“…These transient changes appear to play an important role in the regulation of circulatory system responses during exercise, as NSAID administration can block exercise-induced muscle hyperemia and the cardiovascular pressor reflex (22,25,79). Similarly, increases in 5-LOX-derived plasma LTB 4 have been observed in humans immediately following high-intensity running in some (40), but not all studies (70). In the present study, circulating PGs and LTs (with the exception of TXB 2 ) were unchanged immediately after resistance exercise, but exhibited a delayed peak elevation between ϳ1 and 2 h (PGD 2 , PGE 2 , PGF 2␣ , and LTB 4 ) and 24 h (6-keto-PGF 1␣ ) into recovery.…”

Exercise-induced Bronchospasm In Children

“…Leukotriene LTE4 is found in the urine in exercising individuals [6][7][8]; it counteracts the airway relaxant effect of prostaglandin PGE2 [6,7]. Enhanced transcription of the genes for 5-lipoxygenase and its activating protein (5−lipoxygenaseactivating protein) 2 and 6 h after exercise has been documented [42]. The severity of EIB in Korean children [43] was shown to be influenced by leukotriene C4 synthase promoter polymorphism.…”

Physical stress as a model to study variations in ADAMTS‐13 activity, von Willebrand factor level and platelet activation

“…VWF is a well-documented acute phase protein, and the pro-inflammatory cytokine interleukin (IL)-6 has been reported to cause an irreversible inhibition by proteolytic fragmentation of ADAMTS-13 [12]. We recently showed that physical stress results in a gene expression pattern in circulating blood leukocytes that is very similar to that observed in systemic inflammation [13].…”