TY - JOUR
T1 - Short palate, lung, and nasal epithelial clone-1 is a tightly regulated airway sensor in innate and adaptive immunity
AU - Britto, Clemente J.
AU - Liu, Qing
AU - Curran, David R.
AU - Patham, Bhargavi
AU - Cruz, Charles S.Dela
AU - Cohn, Lauren
PY - 2013/6
Y1 - 2013/6
N2 - Short palate, lung, and nasal epithelial clone-1 (SPLUNC1) is a protein abundantly expressed by the respiratory epitheliumof the proximal lower respiratory tract, a site of great environmental exposure. Previous studies showed that SPLUNC1 exerts antimicrobial effects, regulates airway surface liquid and mucociliary clearance, and suppresses allergic airway inflammation. We studied SPLUNC1 to gain insights into its role in host defense. In the lower respiratory tract, concentrations of SPLUNC1 are high under basal conditions. In models of pneumonia caused by common respiratory pathogens, and in Th1-inducedandTh2-induced airwayinflammation,SPLUNC1secretion is markedly reduced. Pathogen-associated molecular patterns and IFN-g act directly on airway epithelial cells to inhibit SPLUNC1 mRNA expression. Thus, SPLUNC1 is quickly suppressed during infection, in response to an insult on the epithelial surface. These experiments highlight the finely tuned fluctuations of SPLUNC1 in response to exposures in the respiratory tract, and suggest that the loss of SPLUNC1 is a crucial feature of host defense across airbreathing animal species.
AB - Short palate, lung, and nasal epithelial clone-1 (SPLUNC1) is a protein abundantly expressed by the respiratory epitheliumof the proximal lower respiratory tract, a site of great environmental exposure. Previous studies showed that SPLUNC1 exerts antimicrobial effects, regulates airway surface liquid and mucociliary clearance, and suppresses allergic airway inflammation. We studied SPLUNC1 to gain insights into its role in host defense. In the lower respiratory tract, concentrations of SPLUNC1 are high under basal conditions. In models of pneumonia caused by common respiratory pathogens, and in Th1-inducedandTh2-induced airwayinflammation,SPLUNC1secretion is markedly reduced. Pathogen-associated molecular patterns and IFN-g act directly on airway epithelial cells to inhibit SPLUNC1 mRNA expression. Thus, SPLUNC1 is quickly suppressed during infection, in response to an insult on the epithelial surface. These experiments highlight the finely tuned fluctuations of SPLUNC1 in response to exposures in the respiratory tract, and suggest that the loss of SPLUNC1 is a crucial feature of host defense across airbreathing animal species.
KW - Immunity
KW - Inflammation
KW - Innate
KW - Mucosa
KW - SPLUNC1
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UR - http://www.scopus.com/inward/citedby.url?scp=84880986581&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2012-0072OC
DO - 10.1165/rcmb.2012-0072OC
M3 - Article
C2 - 23470624
AN - SCOPUS:84880986581
VL - 48
SP - 717
EP - 724
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 6
ER -