Infection of human respiratory submucosal glands with rhinovirus: effects on cytokine and ICAM-1 production.
To further understand the early biochemical events that occur in infected surface epithelium, we developed for the first time a model in which a respiratory submucosal gland cell population can be infected with rhinovirus (RV). Viral infection was confirmed by demonstrating with PCR that viral titers in supernatants and lysates from infected cells increased with time. Infection by RV14 upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, the major RV receptor, on submucosal gland cells, and it increased production of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor in supernatants. Antibodies to ICAM-1 inhibited RV infection of submucosal gland cells and decreased the production of cytokines after RV infection. Both IL-1alpha and IL-1beta upregulated ICAM-1 mRNA expression and increased susceptibility to RV infection, whereas other cytokines failed to alter ICAM-1 mRNA expression. Furthermore, neutralizing antibodies to IL-1alpha and IL-1beta significantly decreased the viral titers in supernatants and ICAM-1 mRNA expression after RV infection, but a neutralizing antibody to tumor necrosis factor-alpha was without effect. These findings suggest that respiratory submucosal gland cells play an important role in the initial stages of inflammation and provide useful insights into the pathogenesis of RV infection.
Yamaya
M
M
Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai 980-8574, Japan.
Sekizawa
K
K
Suzuki
T
T
Yamada
N
N
Furukawa
M
M
Ishizuka
S
S
Nakayama
K
K
Terajima
M
M
Numazaki
Y
Y
Sasaki
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology / Q000821:virology; D010850:Picornaviridae Infections / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D012229:Rhinovirus / Q000235:genetics; D014132:Trachea / Q000187:drug effects / Q000473:pathology / Q000821:virology*
D000906:Antibodies; D016207:Cytokines; D012333:RNA, Messenger; D012367:RNA, Viral; D018799:Intercellular Adhesion Molecule-1