IL-4 induces production of the lung collectin surfactant protein-D.
BACKGROUND
Surfactant protein (SP)-D is an epithelial cell product of the distal air spaces that aids uptake and clearance of inhaled pathogens and allergens. Allergic airway inflammation significantly increases SP-D levels in the bronchoalveolar lavage fluid in asthmatic patients and mouse models, but the mechanisms involved remain unknown.


OBJECTIVE
To investigate the effects of the TH2-type cytokine IL-4 on SP-D production by isolated pulmonary epithelial cells.


METHODS
Rat type II alveolar epithelial cells were purified and cultured with dexamethasone, cAMP, and isobutyl-1-methylxanthine (DCI). The effects of IL-4 on SP-D expression were investigated at the protein and mRNA levels by means of Western and Northern blot analyses.


RESULTS
In contrast to a lamellar body protein ABCA3 and surfactant protein-A, expression of SP-D significantly declined when cells were cultured in medium alone for 24 hours. The presence of DCI in the culture medium restored SP-D levels, which were enhanced by 2-fold after addition of recombinant IL-4. The enhancing effects of IL-4 were concentration-dependent, with maximum effects observed at 20 ng/mL (1.43 nmol/L). IL-4 did not rescue cycloheximide-induced decrease of intracellular SP-D levels and did not inhibit extracellular release of SP-D. However, IL-4 significantly augmented DCI-induced SP-D mRNA expression by approximately 2.5-fold over control levels.


CONCLUSIONS
IL-4 selectively upregulates SP-D expression, and it may act at the level of mRNA in isolated pulmonary epithelial cells. Since SP-D has a potent anti-inflammatory function, this mechanism may be part of a negative feedback loop providing a regulatory link between adaptive and innate immunity during allergic inflammation.
Pulmonary Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6061, USA.
Yang
Y
Cao
Jian-Qin
JQ
Tao
Sandra R
SR
Bates
Michael F
MF
Beers
Angela
A
Haczku
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D037663:Pulmonary Surfactant-Associated Protein D; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D003907:Dexamethasone; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine