Interleukin-17A mRNA and protein expression within cells from the human bronchoalveolar space after exposure to organic dust.
BACKGROUND
In mice, the cytokine interleukin (IL)-17A causes a local accumulation of neutrophils within the bronchoalveolar space. IL-17A may thereby also contribute to an increased local proteolytic burden. In the current study, we determined whether mRNA for IL-17A is elevated and protein expression of IL-17A occurs locally in inflammatory cells within the human bronchoalveolar space during severe inflammation caused by organic dust. We also assessed the expression of the elastinolytic protease MMP-9 in this airway compartment.


METHODS
Six healthy, non-smoking human volunteers were exposed to organic dust in a swine confinement, a potent stimulus of neutrophil accumulation within the human bronchoalveolar space. Bronchoalveolar lavage (BAL) fluid was harvested 2 weeks before and 24 hours after the exposure and total and differential counts were conducted for inflammatory BAL cells. Messenger RNA for IL-17A was measured using reverse transcript polymerase chain reaction-enzyme linked immunoassay (RT-PCR-ELISA). Intracellular immunoreactivity (IR) for IL-17A and MMP-9, respectively, was determined in BAL cells.


RESULTS
The exposure to organic dust caused more than a forty-fold increase of mRNA for IL-17A in BAL cells. IL-17A immunoreactivity was detected mainly in BAL lymphocytes, and the number of these IL-17A expressing lymphocytes displayed an eight-fold increase, even though not statistically significant. The increase in IL-17A mRNA was associated with a substantial increase of the number of BAL neutrophils expressing MMP-9 immunoreactivity.


CONCLUSIONS
Exposure to organic dust increases local IL-17A mRNA and because there is intracellular expression in BAL lymphocytes, this suggests that IL-17A protein can originate from lymphocytes within the human bronchoalveolar space. The fact that the increased IL-17A mRNA is associated with an increased number of MMP-9-expressing neutrophils is compatible with IL-17A increasing the local proteolytic burden through its neutrophil-accumulating effect.
Ivanov
Stefan
S
Department of Respiratory Medicine and Allergy, Institute for Internal Medicine, Göteborg University, Guldhedsgatan 10A, 413 46 Gothenburg, Sweden. Stefan.Ivanov@lungall.gu.se
Palmberg
Lena
L
Venge
Per
P
Larsson
Kjell
K
Lindén
Anders
A
D000328:Adult; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002478:Cells, Cultured; D004391:Dust; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009930:Organic Chemicals / Q000009:adverse effects*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
D004391:Dust; C508717:IL17A protein, human; D020381:Interleukin-17; D009930:Organic Chemicals; D012333:RNA, Messenger