UP-REGULATION OF CD44 EXPRESSION BY TUMOR-NECROSIS-FACTOR-ALPHA IS NEUTRALIZED BY INTERLEUKIN-10 LANGERHANS CELLS

CD44 is a principal cell-surface receptor for hyaluronate and is found on a wide variety of cells. CD44 plays an important role in lymphocyt e homing, lymphohemopoiesis, and T-cell activation as well as in cell motility and migration, CD44 is expressed on the cell surface of epide rmal Langerhans cells (LC), and is one of the candidates for molecules that are involved in the migratory capability of LC, but little is kn own about its regulatory properties, We examined the modulatory effect s of tumor necrosis factor (TNE)-alpha and interleukin (IL)-10 on the CD44 expression in LC. We found 1) that TNF-alpha significantly up-reg ulated the expression of CD44 in a concentration-dependent manner, 2) that IL-10 down-regulated the expression of CD44 in a concentration-de pendent manner, 3) that the effect of TNF-alpha or IL-10 was readily d etectable as early as 24 h after the initiation of culture, and 4) tha t the simultaneous addition of TNE-alpha and IL-10 mutually neutralize d the effect of each other, These data suggest that in the epidermal m icroenvironment the expression of CD44 in LC may be reciprocally regul ated by TNE-alpha and IL-10, both of which are known to be produced by surrounding keratinocytes.