Effects of secretory leucocyte protease inhibitor on the production of the anti-inflammatory cytokines, IL-10 and transforming growth factor-beta (TGF-beta), by lipopolysaccharide-stimulated macrophages.
We studied the effects of secretory leucocyte protease inhibitor (SLPI) on the production of the anti-inflammatory cytokines, IL-10 and TGF-beta, by lipopolysaccharide (LPS)-stimulated macrophages, using half-sized SLPI (1/2 SLPI) containing the C-terminal domain (Arg58-Ala107). ELISA testing of macrophage culture fluids showed a temporary production of IL-10 by the macrophages in the early phase (24 h) after LPS stimulation at low (1 ng/ml) or high (10 microg/ml) concentrations. On the other hand, TGF-beta production was initiated after day 3 and progressively increased. 1/2 SLPI significantly increased IL-10 and TGF-beta production by macrophages in response to a low dose as well as a high dose of LPS. Reverse transcription-polymerase chain reaction analysis showed that 1/2 SLPI caused a significant increase in the expression of both IL-10 and TGF-beta mRNAs by LPS-stimulated macrophages. Thus, although the profile of macrophage TGF-beta production by LPS-stimulated macrophages is markedly different from that of their IL-10 production, SLPI causes an up-regulation of the production of these anti-inflammatory cytokines by LPS-stimulated macrophages.
Sano
C
C
Department of Microbiology and Immunology and Department of Otorhinolaryngology, Shimane Medical University, Izumo, Shimane, Japan.
Shimizu
T
T
Sato
K
K
Kawauchi
H
H
Tomioka
H
H
D000818:Animals; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000276:immunology* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D053481:Secretory Leukocyte Peptidase Inhibitor; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D008070:Lipopolysaccharides; D008934:Mitogens; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; C506815:Slpi protein, mouse; D016212:Transforming Growth Factor beta; D016753:Interleukin-10