TY - JOUR
T1 - Extracellular regulation of interleukin (IL)-1β through lung epithelial cells and defective IL-1 type II receptor expression
AU - Coulter, Kristin R.
AU - Wewers, Mark D.
AU - Lowe, Melissa P.
AU - Knoell, Daren L.
PY - 1999
Y1 - 1999
N2 - Interleukin (IL)-1β is produced primarily by activated mononuclear phagocytic cells in the lung airway and functions as a potent proinflammatory cytokine. Release of IL-1beta; in the airway microenvironment induces the production of proinflammatory factors from parenchymal airway cells, including IL-8. To study the regulation of lung epithelial cell responsiveness to IL-1β, the human type II-like airway epithelial cell line A549 and primary normal human bronchial epithelial (NHBE) cells were assayed for IL-1-specific response modifiers. Specifically, the IL-1 type I receptor (IL-1RI), IL-1 type II receptor (IL-1RII), TL-1 receptor accessory protein (IL-1RAcP), and IL-1 receptor antagonist (IL-1Ra) were analyzed. Constitutive expression of IL-1RI, IL-1RAcP, and IL-1Ra was detected in both immortalized and primary human airway epithelial cells. Interestingly, a complete absence of IL-1RII expression was demonstrated under all study conditions in both A549 and NHBE cells. Both cell types were responsive to IL-1β at concentrations as low as 50 to 500 pg/ml when measured by IL-8 release into cell supernatants. IL-1β-induced chemokine production and release were inhibited by a 10-to 1,000-fold molar excess of recombinant IL-1RII or IL-1Ra, whereas IL-1RI was a less effective inhibitor. On the basis of our results, we propose that human lung epithelial cells lack the ability to downregulate IL-1β activity extracellularly because of an inability to express IL-1RII. Release of extracellular IL-1 inhibitors, including soluble IL-1Ra and soluble IL-1RII, by other inflammatory cells present in the airway may be critical for regulation of IL-1β activity in the airway microenvironment.
AB - Interleukin (IL)-1β is produced primarily by activated mononuclear phagocytic cells in the lung airway and functions as a potent proinflammatory cytokine. Release of IL-1beta; in the airway microenvironment induces the production of proinflammatory factors from parenchymal airway cells, including IL-8. To study the regulation of lung epithelial cell responsiveness to IL-1β, the human type II-like airway epithelial cell line A549 and primary normal human bronchial epithelial (NHBE) cells were assayed for IL-1-specific response modifiers. Specifically, the IL-1 type I receptor (IL-1RI), IL-1 type II receptor (IL-1RII), TL-1 receptor accessory protein (IL-1RAcP), and IL-1 receptor antagonist (IL-1Ra) were analyzed. Constitutive expression of IL-1RI, IL-1RAcP, and IL-1Ra was detected in both immortalized and primary human airway epithelial cells. Interestingly, a complete absence of IL-1RII expression was demonstrated under all study conditions in both A549 and NHBE cells. Both cell types were responsive to IL-1β at concentrations as low as 50 to 500 pg/ml when measured by IL-8 release into cell supernatants. IL-1β-induced chemokine production and release were inhibited by a 10-to 1,000-fold molar excess of recombinant IL-1RII or IL-1Ra, whereas IL-1RI was a less effective inhibitor. On the basis of our results, we propose that human lung epithelial cells lack the ability to downregulate IL-1β activity extracellularly because of an inability to express IL-1RII. Release of extracellular IL-1 inhibitors, including soluble IL-1Ra and soluble IL-1RII, by other inflammatory cells present in the airway may be critical for regulation of IL-1β activity in the airway microenvironment.
UR - http://www.scopus.com/inward/record.url?scp=0033126398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033126398&partnerID=8YFLogxK
U2 - 10.1165/ajrcmb.20.5.3458
DO - 10.1165/ajrcmb.20.5.3458
M3 - Article
C2 - 10226066
AN - SCOPUS:0033126398
SN - 1044-1549
VL - 20
SP - 964
EP - 975
JO - American journal of respiratory cell and molecular biology
JF - American journal of respiratory cell and molecular biology
IS - 5
ER -