TY - JOUR
T1 - Endotoxin stimulates hepatocyte interleukin-6 production
AU - Panesar, Ninder
AU - Tolman, Kim
AU - Mazuski, John E.
N1 - Funding Information:
Presented in part at the 22nd Annual Symposium of the Association of Veterans Administration Surgeons, Baltimore, MD, April 26–28, 1998. 1This material is based upon work supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs. 2To whom correspondence should be addressed at Department of Surgery, St. Louis University School of Medicine, 3635 Vista Avenue, P.O. Box 15250, St. Louis, MO 63110-0250.
PY - 1999/8
Y1 - 1999/8
N2 - Background. Interleukin-6 (IL-6) is a multifunctional cytokine which mediates many aspects of the acute phase response. Although known to be produced by macrophages and other proinflammatory cells, IL-6 is also released by many types of epithelial cells. The present studies were performed to determine if endotoxin and proinflammatory cytokines stimulate the release of IL-6 from native murine hepatocytes. Methods. Cultured hepatocytes were treated with various concentrations of lipopolysaccharide (LPS), interleukin-1 (IL-1), or tumor necrosis factor (TNF), in the presence or absence of the IL-1 receptor antagonist (IL-1 RA), an anti-TNF antibody, or dexamethasone. Culture supernatants were assayed for murine IL-6 using an ELISA. The cellular source of IL-6 was investigated using immunohistochemical staining. Results. Hepatocyte IL-6 production was significantly increased following treatment with LPS, IL-1, and TNF. Combinations of LPS and these cytokines were synergistic in stimulating IL-6 release. Dexamethasone, but not IL-1 RA or an anti-TNF antibody, inhibited hepatocyte production of IL-6 in response to LPS. Immunohistochemical staining revealed that the hepatocytes, and not contaminating nonparenchymal cells, were the principal source of the IL-6 produced in these cultures. Conclusions. Murine hepatocytes release significant amounts of IL-6 when exposed to endotoxin or proinflammatory cytokines. LPS appears to stimulate hepatocyte IL-6 production directly, and this effect does not appear to be mediated by IL-1 or TNF.
AB - Background. Interleukin-6 (IL-6) is a multifunctional cytokine which mediates many aspects of the acute phase response. Although known to be produced by macrophages and other proinflammatory cells, IL-6 is also released by many types of epithelial cells. The present studies were performed to determine if endotoxin and proinflammatory cytokines stimulate the release of IL-6 from native murine hepatocytes. Methods. Cultured hepatocytes were treated with various concentrations of lipopolysaccharide (LPS), interleukin-1 (IL-1), or tumor necrosis factor (TNF), in the presence or absence of the IL-1 receptor antagonist (IL-1 RA), an anti-TNF antibody, or dexamethasone. Culture supernatants were assayed for murine IL-6 using an ELISA. The cellular source of IL-6 was investigated using immunohistochemical staining. Results. Hepatocyte IL-6 production was significantly increased following treatment with LPS, IL-1, and TNF. Combinations of LPS and these cytokines were synergistic in stimulating IL-6 release. Dexamethasone, but not IL-1 RA or an anti-TNF antibody, inhibited hepatocyte production of IL-6 in response to LPS. Immunohistochemical staining revealed that the hepatocytes, and not contaminating nonparenchymal cells, were the principal source of the IL-6 produced in these cultures. Conclusions. Murine hepatocytes release significant amounts of IL-6 when exposed to endotoxin or proinflammatory cytokines. LPS appears to stimulate hepatocyte IL-6 production directly, and this effect does not appear to be mediated by IL-1 or TNF.
KW - Acute phase proteins
KW - Dexamethasone
KW - Endotoxins
KW - Interleukin- 1 receptor antagonist
KW - Interleukin-1
KW - Interleukin-6
KW - Lipopolysaccharides
KW - Tumor necrosis factor
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U2 - 10.1006/jsre.1999.5648
DO - 10.1006/jsre.1999.5648
M3 - Article
C2 - 10423326
AN - SCOPUS:0032804802
SN - 0022-4804
VL - 85
SP - 251
EP - 258
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -