Effects of secretory leukocyte protease inhibitor on the tumor necrosis factor-alpha production and NF-kappaB activation of lipopolysaccharide-stimulated macrophages |
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Authors: | Sano Chiaki Shimizu Toshiaki Tomioka Haruaki |
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Institution: | Department of Microbiology and Immunology, Shimane Medical, University, Izumo, Shimane 693-8501, Japan. |
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Abstract: | 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. |
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