Dl. Rowell et al., HUMAN HEPATOCYTES EXPRESS AN ARRAY OF PROINFLAMMATORY CYTOKINES AFTERAGONIST STIMULATION OR BACTERIAL INVASION, American journal of physiology: Gastrointestinal and liver physiology, 36(2), 1997, pp. 322-332
Inflammatory cells infiltrate the liver in response to microbial infec
tion or hepatic injury. To assess the potential role hepatocytes may p
lay in initiating or amplifying the acute inflammatory response in the
liver, we used three human hepatocyte cell lines and primary human he
patocyte cultures to characterize the repertoire of cytokines that can
be expressed and regulated in hepatocytes in response to agonist stim
ulation or bacterial infection. As reported herein, a proinflammatory
cytokine gene program that includes C-X-C and C-C chemokines [interleu
kin-8 (IL-8), growth related (GRO)-alpha, GRO-beta, GRO-gamma, epithel
ial neutrophil activating peptide-78 (ENA-78), and RANTES] and the cyt
okines tumor necrosis factor-alpha (TNF-alpha) and macrophage colony s
timulating factor was upregulated in human hepatocytes after stimulati
on with IL-1 alpha or TNF-alpha or bacterial invasion. In contrast, ex
pression of hematopoietic/lymphoid growth factors by the same cells wa
s either downregulated (erythropoietin and stem cell factor) or unchan
ged (IL-7 and IL-15) in response to the identical stimuli. Hepatocytes
did not express cytokines that often are associated with the regulati
on of antigen-specific immune responses (IL-2, IL-4, IL-5, IL-10, IL-1
2p40, IL-13, and interferon-gamma) or genes for several other proinfla
mmatory cytokines [IL-1 alpha, IL-6, monocyte chemotactic protein-1 (M
CP-1), and MCP-S] or hematopoietic growth factors (granulocyte colony
stimulating factor, granulocyte macrophage colony stimulating factor,
IL-3, and IL-11). Together, these studies suggest that hepatocytes can
both initiate and amplify acute inflammatory responses in the liver t
hrough the regulated expression and secretion of a specific array of p
roinflammatory cytokines.