Macrophage colony-stimulating factor (M-CSF) inhibits the decrease in the amount of rRNA and IA beta mRNA in cultured epidermal Langerhans cells of the mouse.

Macrophage colony-stimulating factor (M-CSF) is a keratinocyte-derived cytokine whose function in skin is not completely clarified. We investigated its effects on Langerhans cells by examining the amount of IA beta mRNA, beta-actin mRNA and rRNA per cell, and compared them with the effects of other cytokines such as granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha). After culture for 24 h in the absence of exogenous cytokines, rRNA in Langerhans cells decreased steeply while beta-actin mRNA increased. IA beta mRNA also decreased sharply. These decreases in the amount of rRNA and IA beta mRNA were limited when cytokines were added to the culture medium (in order of efficiency M-CSF > GM-CSF > TNF-alpha), but M-CSF was less potent than GM-CSF in up-regulating beta-actin mRNA (GM-CSF > M-CSF, TNF-alpha). The effect of M-CSF, but not that of GM-CSF, was restricted by simultaneous treatment of cells with TNF-alpha. None of these effects engendered a change in the viability of the Langerhans cells in a 24-hr culture. Reverse-transcribed polymerase chain reaction analysis demonstrated that c-fms, the gene of the M-CSF receptor, was expressed in Langerhans cells, implying the physiological importance of M-CSF in vivo. A protein kinase C activator, TPA, up-regulated the amount of IA beta mRNA, while a protein kinase C inhibitor, H-7, suppressed the effects of all three cytokines. These results suggest that M-CSF, in conjugation with TNF-alpha and GM-CSF, plays an important role in controlling the physiological state of Langerhans cells, probably through the activation of protein kinase C.