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American Journal of Pathology, Vol 142, 1544-1555, Copyright © 1993 by American Society for Investigative Pathology

REGULAR ARTICLES

Comparative lymphokine secretion by cultured normal human cervical keratinocytes, papillomavirus-immortalized, and carcinoma cell lines

CD Woodworth and S Simpson
National Cancer Institute, Laboratory of Biology, Bethesda, MD 20892.

The pathogenesis of cervical human papillomavirus (HPV) infection is influenced by the host's immune response. This response depends upon secretion of specific lymphokines to recruit and activate immune cells at the site of infection. To examine whether cervical cells enhance immune-responsiveness, secretion of lymphokines by cultures of normal cervical cells, HPV-immortalized cervical lines, and carcinoma lines was compared. Normal cervical cells constitutively secreted interleukin- 1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, IL-6, IL-8, tumor necrosis factor-alpha, and granulocyte macrophage colony stimulating factor. Lymphokines were also produced by exo- and endocervical epithelia in vivo. In contrast, four cervical cell lines immortalized by HPV DNAs and three carcinoma lines secreted selected lymphokines at significantly reduced levels. Interferon-gamma induced major histocompatibility class I and II proteins and intercellular adhesion molecule-I in normal cells, but results in immortal or carcinoma lines were variable. These results suggest that cervical epithelial cells have the potential to influence inflammation and immunity in the cervical mucosa. Furthermore, decreased expression of lymphokines and histocompatibility molecules by HPV-immortalized cervical cells suggests that similar alterations might accompany persistent HPV infections in vivo.

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