Effects of secretory leukocyte protease inhibitor on the tumor necrosis factor-alpha production and NF-kappaB activation of lipopolysaccharide-stimulated macrophages.
It has been reported that lipopolysaccharide (LPS)-hyporesponsiveness of macrophages (Mphis) of C3H/HeJ mice with a mutated Lps gene (Lps(d)) is related to high-level expression of secretory leukocyte protease inhibitor (SLPI) in response to LPS, causing suppression of NF-kappaB activation and tumor necrosis factor-alpha (TNF-alpha) production. We thus examined the effects of SLPI on the TNF-alpha production by LPS-stimulated Mphis. Neither intact SLPI nor half-sized SLPI (1/2 SLPI) down-regulated Mphi TNF-alpha production. 1/2 SLPI weakly increased Mphi TNF-alpha production in response to LPS signaling and potentiated the LPS-induced activation of NF-kappaB, especially the binding of p65-p50 heterodimers to the DNA kappaB sites, suggesting that LPS-hyporesponsiveness of Lps(d) Mphis is not due to the overexpression of SLPI.
Sano
Chiaki
C
Department of Microbiology and Immunology, Shimane Medical, University, Izumo, Shimane 693-8501, Japan.
Shimizu
Toshiaki
T
Tomioka
Haruaki
H
D000818:Animals; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D016328:NF-kappa B; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; C506815:Slpi protein, mouse; D014409:Tumor Necrosis Factor-alpha; D004247:DNA