SPLUNC1 regulation in airway epithelial cells: role of Toll-like receptor 2 signaling.
BACKGROUND
Respiratory infections including Mycoplasma pneumoniae (Mp) contribute to various chronic lung diseases. We have shown that mouse short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein was able to inhibit Mp growth. Further, airway epithelial cells increased SPLUNC1 expression upon Mp infection. However, the mechanisms underlying SPLUNC1 regulation remain unknown. In the current study, we investigated if SPLUNC1 production following Mp infection is regulated through Toll-like receptor 2 (TLR2) signaling.


METHODS
Airway epithelial cell cultures were utilized to reveal the contribution of TLR2 signaling including NF-κB to SPLUNC1 production upon bacterial infection and TLR2 agonist stimulation.


RESULTS
Mp and TLR2 agonist Pam3CSK4 increased SPLUNC1 expression in tracheal epithelial cells from wild type, but not TLR2(-/-) BALB/c mice. RNA interference (short-hairpin RNA) of TLR2 in normal human bronchial epithelial cells under air-liquid interface cultures significantly reduced SPLUNC1 levels in Mp-infected or Pam3CSK4-treated cells. Inhibition and activation of NF-κB pathway decreased and increased SPLUNC1 production in airway epithelial cells, respectively.


CONCLUSIONS
Our data for the first time suggest that airway epithelial TLR2 signaling is pivotal in mycoplasma-induced SPLUNC1 production, thus improving our understanding of the aberrant SPLUNC1 expression in airways of patients suffering from chronic lung diseases with bacterial infections.
Department of Medicine, National Jewish Health, and the University of Colorado Denver, Denver, CO, USA. chuhw@njhealth.org
Hong Wei
HW
Chu
Fabienne
F
Gally
Jyoti
J
Thaikoottathil
Yvonne M
YM
Janssen-Heininger
Qun
Q
Wu
Gongyi
G
Zhang
Nichole
N
Reisdorph
Stephanie
S
Case
Maisha
M
Minor
Sean
S
Smith
Di
D
Jiang
Nicole
N
Michels
Glenn
G
Simon
Richard J
RJ
Martin
D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D011019:Pneumonia, Mycoplasma / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
C485599:BPIFA1 protein, human; C119074:Bpifa1 protein, mouse; D006023:Glycoproteins; D010750:Phosphoproteins; C495342:TLR2 protein, human; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2