Cytokines and cellular crosstalk involved in the activation of fat-storing cells.
Based on current knowledge a "3-step cascade model of fat-storing cell activation" is suggested, which implies sequential cross-talk between fat-storing cells, hepatocytes, Kupffer cells, thrombocytes, endothelial cells, and myofibroblasts (transformed fat-storing cells) (Fig. 4). In a preinflammatory phase (I) due to membrane damage (often the initiating event) release of a paracrine acting mitogen from hepatocytes is favoured, which initiates proliferation of fat-storing cells. During the subsequent inflammatory phase (II) cytokines of activated Kupffer cells/macrophages (TGF-beta, TGF-alpha, "lipocyte activating factor" etc.) and of disintegrated platelets (TGF-beta, EGF-like factors, PDGF etc.) are released at the locus of necrosis. TGF-beta, the prototype of a fibrogenic cytokine (102), markedly affects the transformation of fat-storing cells to myofibroblasts. The latter cell type is stimulated during the postinflammatory phase (III) via an autocrine loop by TGF-alpha, TGF-beta, and FGF. In combination with further paracrine stimulation of untransformed fat-storing cells by myofibroblasts the postinflammatory phase potentially contributes to self-perpetuation of fibrogenesis even after cessation of the initiating event (43). In addition to polypeptide mediators, low molecular weight chemical compounds like acetaldehyde, reactive oxygen species, eicosanoids, and lactate are potentially involved in fat-storing cell activation (26). In the network of cytokines, extracellular matrix, and cells several positively and negatively acting regulatory loops are possible.
Gressner
A M
AM
Department of Clinical Chemistry, Philipps University, Marburg, Germany.
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002450:Cell Communication; D016207:Cytokines / Q000494:pharmacology*; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology; D008103:Liver Cirrhosis / Q000209:etiology
D016207:Cytokines