title: Ecrg4 attenuates the inflammatory proliferative response of mucosal epithelial cells to infection.
abstract: We report an inverse relationship between expression of the orphan candidate tumor suppressor gene esophageal cancer related gene 4 (Ecrg4), and the mucosal epithelial cell response to infection in the middle ear (ME). First, we found constitutive Ecrg4 mRNA expression in normal, quiescent ME mucosa that was confirmed by immunostainning of mucosal epithelial cells and immunoblotting of tissue lysates for the 14 kDa Ecrg4 protein. Upon experimental ME infection, Ecrg4 gene expression rapidly decreased by over 80%, between 3 to 48 hrs, post infection. When explants of this infected mucosa were placed in culture and transduced with an adenovirus (AD) encoding Ecrg4 gene (ADEcrg4), the proliferative and migratory responses of mucosal cells were significantly inhibited. ADEcrg4 transduction of control explants from uninfected MEs had no effect on basal growth and migration. Over-expression of Ecrg4 in vivo, by pre-injecting MEs with ADEcrg4 48 hrs prior to infection, prevented the natural down-regulation of Ecrg4, reduced mucosal proliferation and prevented inflammatory cell infiltration normally observed after infection. Taken together, these data support a hypothesis that Ecrg4 plays a role in coordinating the inflammatory and proliferative response to infection of mucosal epithelium suggesting a possible mechanism for its putative anti-tumor activity.
authors.affiliation: Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California, United States of America.
authors.forename: Arwa
authors.initials: A
authors.lastname: Kurabi
authors.forename: Kwang
authors.initials: K
authors.lastname: Pak
authors.forename: Xitong
authors.initials: X
authors.lastname: Dang
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
authors.forename: Brian P
authors.initials: BP
authors.lastname: Eliceiri
authors.forename: Allen F
authors.initials: AF
authors.lastname: Ryan
authors.forename: Andrew
authors.initials: A
authors.lastname: Baird
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D004432:Ear, Middle / Q000276:immunology* / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D005786:Gene Expression Regulation / Q000276:immunology; D005822:Genetic Vectors; D006192:Haemophilus Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D006193:Haemophilus influenzae / Q000502:physiology; D008297:Male; D009092:Mucous Membrane / Q000276:immunology* / Q000382:microbiology; D010033:Otitis Media / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D057057:Serine Proteases / Q000235:genetics / Q000276:immunology*; D014161:Transduction, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: C584405:Ecrg4 protein, rat; D025521:Tumor Suppressor Proteins; D057057:Serine Proteases