title: Gob-5 contributes to goblet cell hyperplasia and modulates pulmonary tissue inflammation.
abstract: Gob-5 is a member of the calcium-activated chloride channel family and has been associated with allergic response in mouse models of pulmonary inflammation. Gene expression of Gob-5 has been shown to be induced in allergic airways and has been strongly associated with mucin gene regulation and goblet cell hyperplasia. We investigated the physiologic role of Gob-5 in murine models of pulmonary inflammation using mice deficient in Gob-5. After sensitization and aerosol challenge with ovalbumin (OVA), Gob-5 knockout mice exhibit significantly increased bronchoalveolar lavage (BAL) inflammation as compared with wild-type controls. The augmented inflammation in BAL consisted predominantly of neutrophils. Examination of perivascular inflammation revealed that tissue inflammation was decreased in OVA-challenged Gob-5-/- mice. OVA-challenged Gob-5 knockout mice also had decreased goblet cell hyperplasia as well as decreased mucus production. These mice also had decreased airway hypersensitivity after cholinergic provocation with methacholine. Gob-5 knockout mice were also challenged via intranasal LPS, a TLR-4 agonist. Gob-5-/- mice responded with increased neutrophilic BAL inflammation and decreased perivascular tissue inflammation as compared with wild-type controls. There was little effect on goblet cell hyperplasia and mucus production after LPS challenge. These observations reinforce findings that associate Gob-5 with goblet cell hyperplasia and mucus production in the allergic immune response, but also implicate Gob-5 in the regulation of tissue inflammation in the innate immune response.
authors.affiliation: Respiratory Diseases, Wyeth Research, Cambridge, Massachusetts 02140, USA. along@wyeth.com
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Long
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Sypek
authors.forename: Roger
authors.initials: R
authors.lastname: Askew
authors.forename: Susan C
authors.initials: SC
authors.lastname: Fish
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Mason
authors.forename: Cara M M
authors.initials: CM
authors.lastname: Williams
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Goldman
mesh_terms: D000403:Airway Resistance; D000818:Animals; D000941:Antigens / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000378:metabolism; D018118:Chloride Channels / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009088:Mucoproteins / Q000235:genetics / Q000502:physiology*; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000633:toxicity; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*
chemical_list: D000941:Antigens; D018925:Chemokines; D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D008070:Lipopolysaccharides; D009088:Mucoproteins; D010047:Ovalbumin