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 rat gastric epithelial RGM1 monolayers was investigated. The repair of wounds 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 treatment of the cells with the macrophage supernatant, spontaneous and TGF-alpha-stimulated restoration was inhibited in a time- and concentration-dependent manner. After 24 hr, TGF-alpha-enhanced restoration was eliminated completely by the supernatant at 10(6) cells/mL. Similarly, the macrophage supernatant suppressed the spontaneous and TGF-alpha-stimulated DNA syntheses in a concentration-dependent manner. The macrophage supernatant at 10(6) cells/mL contained 0.4 ng/mL of interleukin-1beta (IL-1beta). Interleukin-1 receptor antagonist (IL-1RA) reversed the inhibition induced by the macrophage supernatant in a concentration-dependent manner. Nonetheless, pretreatment with IL-1RA had no effects on the spontaneous and TGF-alpha-stimulated DNA syntheses. Reverse transcription-polymerase chain reaction analysis revealed that RGM1 cells express mRNA for IL-1 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 monolayers. The inhibitory effects of the supernatant are suggested to be partially mediated through a IL-1beta/IL-1 receptor type 1 pathway.
Nakamura
E
E
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan. enakamur@caregroup.harvard.edu
Takahashi
S
S
Ishikawa
M
M
Okabe
S
S
D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000293:injuries* / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology*
D001685:Biological Factors; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D016212:Transforming Growth Factor beta; D004247:DNA