title: Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection.
abstract: Human rhinovirus (HRV) infections trigger exacerbations of asthma and chronic obstructive pulmonary disease (COPD) and are associated with lymphocytic infiltration of the airways. We demonstrate that infection of primary cultures of human airway epithelial cells, or of the BEAS-2B human bronchial epithelial cell line, with human rhinovirus type 16 (HRV-16) induces expression of CXCL10 [IFN-gamma-inducible protein 10 (IP-10)], a ligand for the CXCR3 receptor found on activated type 1 T lymphocytes and natural killer cells. IP-10 mRNA reached maximal levels 24 h after HRV-16 infection then declined, whereas protein levels peaked 48 h after infection with no subsequent new synthesis. Cytosolic levels of AU-rich factor 1, a protein associated with mRNA destabilization, increased beginning 24 h after HRV-16 infection. Generation of IP-10 required virus capable of replication but was not dependent on prior induction of type 1 interferons. Transfection of synthetic double-stranded RNA into epithelial cells induced robust production of IP-10, whereas transfection of single-stranded RNA had no effect. Induction of IP-10 gene expression by HRV-16 depended upon activation of NF-kappaB, as well as other transcription factor recognition sequences further upstream in the IP-10 promoter. In vivo infection of human volunteers with HRV-16 strikingly increased IP-10 protein in nasal lavages during symptomatic colds. Levels of IP-10 correlated with symptom severity, viral titer, and numbers of lymphocytes in airway secretions. Thus IP-10 may play a role in the pathogenesis of HRV-induced colds and in HRV-induced exacerbations of COPD and asthma.
authors.affiliation: Respiratory Research Group and Department of Physiology and Biophysics, University of Calgary, Alberta.
authors.forename: Jason C L
authors.initials: JC
authors.lastname: Spurrell
authors.forename: Shahina
authors.initials: S
authors.lastname: Wiehler
authors.forename: Raza S
authors.initials: RS
authors.lastname: Zaheer
authors.forename: Scherer P
authors.initials: SP
authors.lastname: Sanders
authors.forename: David
authors.initials: D
authors.lastname: Proud
mesh_terms: D001249:Asthma / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D005786:Gene Expression Regulation; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010850:Picornaviridae Infections / Q000378:metabolism* / Q000821:virology; D011401:Promoter Regions, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000821:virology; D012330:RNA, Double-Stranded / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012137:Respiratory System / Q000166:cytology / Q000378:metabolism*; D012229:Rhinovirus; D014162:Transfection
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D012333:RNA, Messenger