Rhinovirus infection of primary cultures of human tracheal epithelium: role of ICAM-1 and IL-1b

Terajima, Masanori, Mutsuo Yamaya, Kiyohisa Sekizawa, Shoji Okinaga, Tomoko Suzuki, Norihiro Yamada, Katsutoshi Nakayama, Takashi Ohrui, Takeko Oshima, Yoshio Numazaki, and Hidetada Sasaki. Rhinovirus infection of primary cultures of human tracheal epithelium: role of ICAM-1 and IL-1b. Am. J. Physiol. 273 (Lung Cell. Mol. Physiol. 17): L749–L759, 1997.—Exacerbations of asthma are often associated with respiratory infection caused by rhinoviruses. To study the effects of rhinovirus infection on respiratory epithelium, a primary target for respiratory viruses, human rhinovirus (HRV)-2 and HRV-14 were infected to primary cultures of human tracheal epithelial cells. Viral infection was confirmed by showing that viral titers of supernatants and lysates from infected cells increased with time and by polymerase chain reaction. HRV-2 and HRV-14 infections upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, the major rhinovirus receptor, on epithelial cells, and they increased the production of interleukin (IL)-1b, IL-6, IL-8, and tumor necrosis factor (TNF)-a in supernatants. Antibodies to ICAM-1 inhibited HRV-14 infection of epithelial cells and decreased the production of cytokines after HRV-14 infection, but they did not alter HRV-2 infection-induced production of cytokines. IL-1b upregulated ICAM-1 mRNA expression and increased susceptibility to HRV-14 infection, whereas other cytokines failed to alter ICAM-1 mRNA expression. Furthermore, a neutralizing antibody to IL-1b significantly decreased viral titers of supernatants and ICAM-1 mRNA expression after HRV-14 infection, but a neutralizing antibody to TNF-a was without effect. Immunohistochemical studies revealed that both HRV-14 infection and IL-1b increased ICAM-1 expression on cultured epithelial cells. These findings imply that HRV-14 infection upregulated ICAM-1 expression on epithelial cells through increased production of IL-1b, thereby increasing susceptibility to infection. These events may be important for amplification of airway inflammation after viral infection in asthma.