Rhinovirus replication causes RANTES production in primary bronchial epithelial cells.
The mechanisms by which rhinovirus (RV) infections produce lower airway symptoms in asthmatic individuals are not fully established. To determine effects of RV infection on lung epithelial cells, primary human bronchial epithelial (BE) cells were infected with either RV16 or RV49, and viral replication, cell viability, and cell activation were measured. Both viral serotypes replicated in BE cells at 33 degrees C (DeltaTCID50 / ml = 2 to 2.5 log units) and at 37 degrees C (DeltaTCID50 /ml = 1.6 log units), but only high doses of RV49 (10(6) TCID50 /ml) caused cytopathic effects and reduced cell viability. In addition, regulated on activation, normal T cells expressed and secreted (RANTES) secretion was increased in epithelial cells infected with RV16 or RV49 (243 and 398 pg/ml versus 13 pg/ml uninfected control cells), and a similar pattern was seen for RANTES messenger RNA. RV infection also caused increased secretion of interleukin-8 and granulocyte macrophage colony-stimulating factor, but did not alter expression of either intercellular adhesion molecule-1 or human leukocyte-associated antigen-DR. These observations suggest that RVs can replicate in lower airway cells in vivo, and support epidemiologic studies that link RV with lower respiratory illnesses. Further, RV-induced secretion of RANTES and other cytokines could trigger antiviral immune responses in vivo, but these effects could also contribute to the pathogenesis of respiratory symptoms in subjects with asthma.
Schroth
M K
MK
Department of Pediatrics, University of Wisconsin, Madison, Wisconsin 53792-4108, USA. mschroth@facstaff.wisc.edu
Grimm
E
E
Frindt
P
P
Galagan
D M
DM
Konno
S I
SI
Love
R
R
Gern
J E
JE
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001249:Asthma / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007249:Inflammation; D008077:Lipoproteins, LDL / Q000494:pharmacology; D012229:Rhinovirus / Q000378:metabolism* / Q000472:pathogenicity; D013696:Temperature; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D018946:Chemokine CCL5; D008077:Lipoproteins, LDL; D006854:Hydrocortisone