Production of interleukin-1 and tumor necrosis factor by cisplatin-treated murine peritoneal macrophages.
Supernatants collected from cisplatin-treated macrophages demonstrated enhanced cytotoxicity against actinomycin-D-treated L929 cells and also enhanced the thymocyte proliferation in response to concanavalin A, showing that cisplatin-treated macrophages release interleukin-1 (IL-1) and tumor necrosis factor (TNF) into the culture supernatant. The supernatant collected from untreated macrophages showed little TNF and IL-1 activity. The release of TNF and IL-1 was observed to be dependent on the dose and duration of cisplatin treatment. Medium alone containing cisplatin did not enhance thymocyte proliferation and had little cytotoxic effect on actinomycin-D-treated L929 cells. Cisplatin-treated macrophage culture supernatants were chromatographed over a Superose 12 column on an FPLC system. TNF activity eluted in two major peaks with apparent molecular weights of 50-55 and 15-20 kilodaltons, respectively. The kinetics of IL-1 release was also studied. Maximum production and release of IL-1 were observed up to 24 h after cisplatin treatment and then gradually declined. Freeze-thaw lysates of cisplatin-treated macrophages also showed enhanced IL-1 activity. Paraformaldehyde (PFA)-fixed cisplatin-treated macrophages showed significantly enhanced cytotoxic activity against L929 cells as compared to PFA-fixed untreated macrophages. PFA-fixed cisplatin-treated macrophages also enhanced thymocyte proliferation. These results suggest that cisplatin treatment of murine macrophages also results in increased expression of membrane-associated IL-1 and TNF activity.
Singh
R K
RK
Department of Zoology, Banaras Hindu University, Varanasi, India.
Sodhi
A
A
Singh
S M
SM
D000818:Animals; D002850:Chromatography, Gel; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010529:Peritoneal Cavity / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000302:isolation & purification
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D002945:Cisplatin