Regulation of cell-surface receptor expression and proliferation of a human transformed keratinocyte cell line by different classes of immunomodulators

Abstract

Previous researchers have emphasized the role of Mycobacterium vaccae, muramyl dipeptides and interferon-γ, in modulating immune responses and in promoting the interaction between innate and adaptive immunity. The three immunomodulators are known to exert their immune effects by different mechanisms, to interact with target cells via different receptors and to induce an adjuvant effect. Administration of these immunomodulators to experimental animals or to Man has been shown to produce beneficial outcome in the management of certain infectious and allergic diseases as well as cancer. Despite the wide implication of Mycobacterium vaccae, and muramyl dipeptides in enhancing the immune recognition and elimination of pathogens, their ability to regulate the function of keratinocytes has not been investigated. On the other hand, only few studies have addressed the response of keratinocytes or keratinocyte cell lines to interferon-γ with few effects reported on transformed cells. The aim of this study is to investigate the effects of Mycobacterium vaccae, muramyl dipeptides and interferon-γ on the expression of a series of cellular receptors in a human transformed keratinocyte cell line, namely HaCaT cells. Some of the immunophenotypic studies were also carried out, for comparative evaluation, on HepG2 cells originating from a human hepatocellular carcinoma. In addition, the ability of each of the three immunomodulators to regulate the proliferative capacity of HaCaT cells was also addressed. Our results clearly demonstrate the inability of Mycobacterium vaccae and of muramyl dipeptide to induce or to up-regulate the HaCaT cell surface expression of a battery of adhesion molecules, of co-stimulatory receptors, and of cytokine and chemokine receptors as measured by flow cytometry. Similarly, no effect could be noted, by these two immunomodulators, on regulating the proliferative potential of the transformed keratinocyte cells. In contrast, interferon-γ shows an ability to up-regulate the expression of a selected set of surface receptors, to down-regulate the expression of its own receptor and to induce significant inhibition of HaCaT cell proliferation. The data obtained will pave the way for a rational selection of classes of immunomodulators to target the function of keratinocytes.