Respiratory syncytial virus in allergic lung inflammation increases Muc5ac and gob-5.
Respiratory syncytial virus (RSV) is associated with wheezing and childhood asthma. We previously reported that RSV infection prolongs methacholine-induced airway hyperresponsiveness in ovalbumin (OVA)-sensitized mice. In addition, allergically sensitized RSV-infected (OVA/RSV) mice had more abundant airway epithelial mucus production compared with OVA mice 14 days after infection, whereas there was almost no mucus in mice that were only RSV infected. We hypothesized that this increased mucus was associated with mucosal expression of Muc5ac, a mucus gene expression in airways, and gob-5, a member of the Ca(2)(+)-activated chloride channel family. By histochemical analysis, we found that there was significantly increased staining for gob-5 and Muc5ac in the airways of OVA/RSV mice compared with either OVA mice or allergically sensitized mice that were challenged with inactivated RSV, and virtually no detectable staining in the RSV group. These findings were confirmed by Western blot analysis. The increased mucus expression in the OVA/RSV group was associated with increased lung levels of interleukin-17, a factor known to stimulate airway mucin gene expression. The impact of virus infection combined with allergic inflammation on mucus production may partially explain the more severe disease and airway hyperresponsiveness associated with RSV in the setting of atopy.
Hashimoto
Koichi
K
Vanderbilt University, School of Medicine, Nashville, Tennessee 37232, USA.
Graham
Barney S
BS
Ho
Samuel B
SB
Adler
Kenneth B
KB
Collins
Robert D
RD
Olson
Sandra J
SJ
Zhou
Weisong
W
Suzutani
Tatsuo
T
Jones
Phillip W
PW
Goleniewska
Kasia
K
O'Neal
Jamye F
JF
Peebles
R Stokes
RS
D000818:Animals; D018118:Chloride Channels / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020381:Interleukin-17 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism*; D009088:Mucoproteins / Q000378:metabolism*; D010047:Ovalbumin; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012136:Respiratory Syncytial Viruses
D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D016207:Cytokines; D020381:Interleukin-17; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; D009088:Mucoproteins; D010047:Ovalbumin