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IL-17-producing T lymphocytes in lung tissue and in the bronchoalveolar space after exposure to endotoxin from Escherichia coli in vivo - effects of anti-inflammatory pharmacotherapy.

Prause, Olof, 1973 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
Bossios, Apostolos, 1969 (författare)
Gothenburg University,Göteborgs universitet,Krefting Research Centre
Silverpil, Elin, 1978 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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Ivanov, Stefan, 1974 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
Bozinovski, Steven (författare)
Vlahos, Ross (författare)
Sjöstrand, Margareta, 1947 (författare)
Gothenburg University,Göteborgs universitet,Krefting Research Centre
Anderson, Gary P (författare)
Lindén, Anders, 1961 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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 (creator_code:org_t)
Elsevier BV, 2009
2009
Engelska.
Ingår i: Pulmonary pharmacology & therapeutics. - : Elsevier BV. - 1094-5539. ; 22:3, s. 199-207
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Interleukin (IL)-17 may play a critical role for the innate immune response in mammals. However, little is known about its production in T lymphocytes in comparison with other cells, in lung tissue and in the bronchoalveolar space in vivo. Even less is known about the effects of anti-inflammatory pharmacotherapy on this IL-17 production. In this study on mice we show that one single, intranasal exposure to endotoxin from Escherichia coli increases extracellular IL-17 protein in bronchoalveolar (BAL) samples during 3 days, and is accompanied by a local increase in neutrophils and other inflammatory cells. This endotoxin exposure also elevates IL-17 mRNA in lung tissue samples. Moreover, after endotoxin exposure, the absolute number of CD3-positive cells containing intracellular IL-17 protein is increased as well; from a moderate cell number in lung tissue samples and from virtually none in BAL samples; with the number in lung tissue exceeding that observed in BAL samples. Notably, we also demonstrate that among the cells that contain intracellular IL-17 protein after endotoxin exposure, the percentage of CD3-positive cells is similar to that of CD3-negative cells in lung tissue. In contrast, CD3-negative cells dominate among IL-17-containing cells in BAL samples. A high systemic dose of a glucocorticoid receptor agonist attenuates the endotoxin-induced increase in extracellular IL-17 protein in BAL samples, IL-17 mRNA in lung tissue samples, and in IL-17-containing CD3-positive cells in BAL and lung tissue samples. This is also true for the endotoxin-induced accumulation of neutrophils and other inflammatory BAL cells in vivo. A systemic dose of a calcineurin phosphatase inhibitor exerts a less complete and more selective effect on the endotoxin-induced increase in extracellular IL-17 protein and on neutrophils in BAL samples. In vitro, endotoxin also increases extracellular IL-17 protein in a co-culture of CD3-positive spleen cells and adherent mononuclear BAL cells; an increase that was inhibited by a glucocorticoid as well as by a calcineurin phosphatase inhibitor. In conclusion, endotoxin-induced IL-17 production and release from T lymphocytes originates from cells that reside in lung tissue and from cells that have been recruited to the bronchoalveolar space. In both compartments, there is also a substantial number of cells other than T lymphocytes that contain IL-17 after endotoxin exposure. The sustained IL-17 production from T lymphocytes and the associated neutrophil accumulation may be inhibited non-selectively through glucocorticoid receptor stimulation and more selectively through calcineurin phosphatase inhibition.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

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