| 1. |
- Ivanov, Stefan, 1974, et al.
(författare)
-
Functional relevance of the IL-23-IL-17 axis in lungs in vivo.
- 2007
-
Ingår i: American journal of respiratory cell and molecular biology. - 1044-1549. ; 36:4, s. 442-51
-
Tidskriftsartikel (refereegranskat)abstract
- It is known that interleukin (IL)-23, an IL-12-family cytokine, can be released by certain antigen-presenting cells in response to bacterial pathogens. Recent in vitro studies indicate that this cytokine stimulates a unique subset of CD4 cells, the T helper cell (Th)17 subset, to produce and release the proinflammatory cytokine IL-17. However, it has not been known whether this is an action of IL-23 per se that has bearing for the early innate response in lungs in vivo and whether there is an IL-23-responsive population of IL-17-producing CD4 cells in the bronchoalveolar space. We now present evidence that IL-23 can be involved in the early innate response to both gram-negative and gram-positive bacterial products in the lungs: Recombinant IL-23 protein per se accumulates inflammatory cells in the bronchoalveolar space in part via endogenous production of IL-17, and this IL-17 production occurs locally in IL-23-responsive CD4 cells. This IL-17 response to IL-23 occurs without any pronounced impact on Th1/Th2 polarization. Moreover, recombinant IL-23 protein increases the local MMP-9 activity, which is generated by neutrophils mainly. CD4 cells in the lungs may thus respond to IL-23 from antigen-presenting cells exposed to gram-negative and gram-positive pathogens and thereby reinforce the early innate response. These findings support that IL-23 and IL-17 form a functionally relevant "immunological axis" in the lungs in vivo.
|
|
| 2. |
- Prause, Olof, 1973, et al.
(författare)
-
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.
- 2009
-
Ingår i: Pulmonary pharmacology & therapeutics. - : Elsevier BV. - 1094-5539. ; 22:3, s. 199-207
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 3. |
- Riise, Gerdt C., 1956, et al.
(författare)
-
Increased net gelatinase but not serine protease activity in bronchiolitis obliterans syndrome.
- 2010
-
Ingår i: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - : Elsevier BV. - 1557-3117. ; 29:7, s. 800-7
-
Tidskriftsartikel (refereegranskat)abstract
- Bronchiolitis obliterans syndrome (BOS) is the main long-term complication after lung transplantation. Previous studies indicate that neutrophil mobilization causes high protease concentrations in the lung allograft during BOS. This study assessed net protease activity and the functional aspect of proteases in BOS.
|
|
| 4. |
- Vlahos, Ross, et al.
(författare)
-
Neutralizing granulocyte/macrophage colony-stimulating factor inhibits cigarette smoke-induced lung inflammation.
- 2010
-
Ingår i: American journal of respiratory and critical care medicine. - 1535-4970. ; 182:1, s. 34-40
-
Tidskriftsartikel (refereegranskat)abstract
- Cigarette smoke is the major cause of chronic obstructive pulmonary disease (COPD), and there is currently no satisfactory therapy to treat people with COPD. We have previously shown that granulocyte/macrophage colony-stimulating factor (GM-CSF) regulates lung innate immunity to LPS through Akt/Erk activation of nuclear factor-kappaB and activator protein (AP)-1.
|
|
