Effects of alpha and beta interferons on cultured human keratinocytes

Interferons (IF) are a family of glycoproteins known for their antiviral activity and the ability to inhibit growth and alter behavior of various normal and transformed cell types, both in vivo and in vitro. Because cultured human keratinocytes (HK) produce IF in response to viral infection, we undertook studies of alpha-IF and beta-IF effects on HK. Cloned human IF were added at time of seeding and at each feeding to paired dishes of keratinocytes maintained in serum-free hormone-supplemented medium. At 7 days significant inhibition of growth was observed for both alpha-IF and beta-IF, as determined by cell counts, total protein, and appearance of stained colonies, and was sustained for at least two weeks during continuous IF exposure. The inhibition was substantially blocked by prior addition of cholera toxin to the medium, consistent with competition for a common cell surface receptor. Growth of a single human epidermal carcinoma cell line was much less affected by IF than was growth of the normal keratinocytes. IF also promoted terminal differentiation of keratinocytes as assessed by desquamation rate of cells from the colony surface and by proportion of total cells having cornified envelopes. IF effect on both growth and differentiation was completely reversible within days of its removal from medium. These findings suggest that IF may function as a physiologic regulator of epidermal growth in vivo with properties of a negative growth factor or chalone.