Inhibitory effect of macrophage derived factors on the recovery of wounds induced in rat gastric epithelial monolayers

The effect of macrophage supernatant on the recovery of wounds induced in r at gastric epithelial RGM1 monolayers was investigated. The repair of wound s induced in the monolayers of RGM1 cells was accelerated time-dependently by 10 ng/mL of transforming growth factor-alpha (TGF-alpha). TGF-alpha also significantly stimulated DNA synthesis in RGM1 cells for 24 hr. Upon treat ment of the cells with the macrophage supernatant, spontaneous and TGF-alph a-stimulated restoration was inhibited in a time- and concentration-depende nt manner. After 24 hr, TGF-alpha enhanced restoration was eliminated compl etely by the supernatant at 10(6) cells/ml. Similarly, the macrophage super natant suppressed the spontaneous and TGF-cr stimulated DNA syntheses in a concentration-dependent manner. The macrophage supernatant at 106 cells/mL contained 0.4 ng/mL of interleukin-1 beta (IL 1 beta). Interleukin-1 recept or antagonist (IL-1RA) reversed the inhibition induced by the macrophage su pernatant in a concentration dependent manner. Nonetheless, pretreatment wi th IL-1RA had no effects on the spontaneous and TGF-alpha-stimulated DNA sy ntheses. Reverse transcription-polymerase chain reaction analysis revealed that RGM1 cells express mRNA for IL-I receptor type 1, but not for type 2. These results indicate that macrophages can inhibit the spontaneous and TGF -alpha-stimulated recovery of wounds induced in gastric epithelial monolaye rs. The inhibitory effects of the supernatant are suggested to be partially mediated through a IL-1 beta/IL-1 receptor type 1 pathway. (C) 1999 Etsevi er Science Inc.