title: Rotavirus stimulates IL-8 secretion from cultured epithelial cells.
abstract: Rotavirus is the most important cause of severe gastroenteritis in children worldwide. We have investigated cytokine responses to rotavirus infection of cultured intestinal epithelial cells. Interleukin 8 (IL-8) is a chemotactic and cell-activating cytokine that is synthesized by epithelial cells and induced in response to bacterial enteric pathogens. Rotavirus inoculation increased IL-8 mRNA levels in cultured intestinal epithelial cells within 2 hr of infection. IL-8 secretion increased 10(2)- to 10(3)-fold by 8 hr postinfection. Secretion of TNF alpha or IL-1 beta, cytokines which themselves increase IL-8 secretion, was not induced by rotavirus, nor was that of TNF alpha, IFN alpha, IFN gamma, or IL-6. Neutralizing antibodies to TNF alpha or IL-1 alpha/beta did not affect the IL-8 response. Secretion of IL-8 was dependent on an intact viral capsid, as single-shell particles were inert. Neutralizing monoclonal antibodies (vp7-specific) that do not block cell attachment did block rotavirus stimulation of IL-8 secretion, indicating that attachment to the cell surface is not a sufficient stimulus to induce IL-8. Genetically inactivated rotavirus was also effective for IL-8 induction, indicating that viral replication was not required. These data suggest that epithelial cytokine IL-8 may be an important mediator of the host response to viral gastroenteritis pathogens such as rotavirus.
authors.affiliation: Northport Veterans Affairs Medical Center, New York 11768, USA.
authors.forename: R
authors.initials: R
authors.lastname: Sheth
authors.forename: J
authors.initials: J
authors.lastname: Anderson
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: B
authors.initials: B
authors.lastname: Oh
authors.forename: S J
authors.initials: SJ
authors.lastname: Hempson
authors.forename: E
authors.initials: E
authors.lastname: Rollo
authors.forename: E R
authors.initials: ER
authors.lastname: Mackow
authors.forename: R D
authors.initials: RD
authors.lastname: Shaw
mesh_terms: D000818:Animals; D001483:Base Sequence; D018938:Caco-2 Cells; D002213:Capsid / Q000276:immunology; D002460:Cell Line; D017931:DNA Primers; D003673:Defective Viruses / Q000276:immunology; D019073:HT29 Cells; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D012333:RNA, Messenger; D012401:Rotavirus / Q000276:immunology* / Q000502:physiology; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D016209:Interleukin-8; D012333:RNA, Messenger