The IL (interleukin)-6-type
cytokines IL-6,
IL-11, LIF (leukaemia inhibitory factor), OSM (
oncostatin M),
ciliary neurotrophic factor, cardiotrophin-1 and
cardiotrophin-like cytokine are an important family of mediators involved in the regulation of the
acute-phase response to injury and
infection. Besides their functions in
inflammation and the immune response, these
cytokines play also a crucial role in haematopoiesis, liver and neuronal regeneration, embryonal development and fertility. Dysregulation of IL-6-type
cytokine signalling contributes to the onset and maintenance of several diseases, such as
rheumatoid arthritis,
inflammatory bowel disease,
osteoporosis,
multiple sclerosis and various types of
cancer (e.g.
multiple myeloma and
prostate cancer). IL-6-type
cytokines exert their action via the signal transducers gp (
glycoprotein) 130, LIF receptor and OSM receptor leading to the activation of the JAK/STAT (
Janus kinase/signal transducer and activator of transcription) and MAPK (
mitogen-activated protein kinase) cascades. This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type
cytokine signal transduction. Emphasis is put on the termination and modulation of the JAK/STAT signalling pathway mediated by
tyrosine phosphatases, the SOCS (suppressor of
cytokine signalling) feedback inhibitors and PIAS (
protein inhibitor of activated STAT)
proteins. Also the cross-talk between the JAK/STAT pathway with other signalling cascades is discussed.