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Id Subject Object Predicate Lexical cue
T19 0-16 Sentence denotes Editors' Summary
T20 18-28 Sentence denotes Background
T21 29-116 Sentence denotes The immune system protects the human body from viruses, bacteria, parasites, and fungi.
T22 117-392 Sentence denotes When one of these foreign invaders enters the body, immune system cells called T lymphocytes recognize specific molecules on the invader's surface and release chemical messengers (cytokines) that recruit and activate other types of immune cell, which then attack the invader.
T23 393-624 Sentence denotes Sometimes, however, the immune system responds to a normally harmless material (for example, house-dust mites or grass pollen; scientists call these materials allergens) and triggers an allergic disease such as asthma or hay fever.
T24 625-811 Sentence denotes Contact with an allergen activates a type of T lymphocyte called a T helper-2 (Th2) cell that subsequently makes (expresses) three cytokines called interleukin-4 (IL-4), IL-5, and IL-13.
T25 812-917 Sentence denotes These cytokines ultimately cause inflammation (swelling) of the part of the body exposed to the allergen.
T26 918-1050 Sentence denotes Corticosteroids, which suppress the expression of cytokines by Th2 cells, are often used to treat inflammation in allergic diseases.
T27 1051-1292 Sentence denotes Other treatments for these common conditions—about 50 million people in the US have an allergic disease—include minimizing exposure to allergens and diminishing the response of the immune system to allergens by using various immunotherapies.
T28 1294-1318 Sentence denotes Why Was This Study Done?
T29 1319-1463 Sentence denotes Scientists know that corticosteroids reduce allergic inflammation by binding to proteins in immune system cells called glucocorticoid receptors.
T30 1464-1665 Sentence denotes After binding to a corticosteroid, these receptors move into the nucleus of the cell (the part of the cell that contains its genes), where they suppress the expression of certain proinflammatory genes.
T31 1666-1757 Sentence denotes However, it is still not known how corticosteroids inhibit the expression of Th2 cytokines.
T32 1758-1880 Sentence denotes A key regulator of the expression of these cytokines and of allergic inflammation is a transcription factor called GATA-3.
T33 1881-2025 Sentence denotes Transcription factors are proteins that control the expression of other proteins by binding to specific sequences in the genes that encode them.
T34 2026-2250 Sentence denotes In this study, the researchers try to discover more about how corticosteroids reduce allergic inflammation by investigating the effects of the corticosteroid fluticasone on the regulation of GATA-3 activity in T lymphocytes.
T35 2252-2289 Sentence denotes What Did the Researchers Do and Find?
T36 2290-2529 Sentence denotes Transcription factors have to move into the nucleus of cells (so-called nuclear translocation) to control the expression of their target genes, so the researchers first asked whether fluticasone affects the cellular localization of GATA-3.
T37 2530-2693 Sentence denotes Fluticasone treatment of activated T lymphocytes growing in dishes, they report, inhibited the nuclear translocation of GATA-3 and reduced Th2 cytokine expression.
T38 2694-2945 Sentence denotes Other experiments showed that the inhibition of GATA-3 nuclear translocation was partly caused by competition between the glucocorticoid receptor bound to fluticasone and GATA-3 for binding to importin-α, a protein that is required for nuclear import.
T39 2946-3034 Sentence denotes However, fluticasone also prevented the nuclear translocation of GATA-3 in a second way.
T40 3035-3135 Sentence denotes Before GATA-3 can bind to importin-α, phosphate groups have to be added to specific sites in GATA-3.
T41 3136-3359 Sentence denotes This “phosphorylation” requires an enzyme called p38 MAP kinase, and the researchers found that fluticasone treatment of activated T lymphocytes induced the expression of MAP kinase phophatase-1, a p38 MAP kinase inhibitor.
T42 3360-3582 Sentence denotes Finally, when the researchers treated seven patients with mild asthma with inhaled fluticasone, they found that fluticasone also inhibited GATA-3 nuclear translocation in the lymphocytes circulating in the patients' blood.
T43 3584-3612 Sentence denotes What Do These Findings Mean?
T44 3613-3820 Sentence denotes These findings, obtained both in the laboratory and in patients, suggest that corticosteroids inhibit the expression of Th2 cytokines and thus reduce allergic inflammation through two interacting mechanisms.
T45 3821-4100 Sentence denotes They suggest that corticosteroids prevent the nuclear translocation of GATA-3, a key regulator of Th2 cytokine expression, by competing with GATA-3 for binding to importin-α and by preventing the phosphorylation of GATA-3, a modification that allows GATA-3 to bind to importin-α.
T46 4101-4421 Sentence denotes This dual mechanism of corticosteroid action may help to explain why these drugs are so effective in the treatment of allergic diseases, although further experiments are needed to show that the lymphocytes resident at sites of allergic inflammation respond to corticosteroids in the same way as lymphocytes in the blood.
T47 4422-4589 Sentence denotes Finally, these findings suggest that the interaction between phosphorylated GATA-3 and importin-α might be a potential target for new treatments for allergic diseases.
T48 4591-4613 Sentence denotes Additional Information
T49 4614-4733 Sentence denotes Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000076.
T50 4734-5065 Sentence denotes The US National Institute of Allergy and Infectious Diseases provides information on allergic diseases and a simple description of the immune system The UK National Health Service Choices service provides information about allergies Links to other information about allergies are available from MedlinePlus (in English and Spanish)