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Int J Biol Sci. 2012;8(9):1267-80. doi: 10.7150/ijbs.4828. Epub 2012 Oct 25.

The pathological and physiological roles of IL-6 amplifier activation.

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  • 1Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, and WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.


The NFκB-triggered positive feedback loop for IL-6 signaling in type 1 collagen+ non-immune cells (IL-6 amplifier) was first discovered to be a synergistic signal that is activated following IL-17A and IL-6 stimulation in type 1 collagen+ non-immune cells. Subsequent disease models have shown that it can also be stimulated by the simultaneous activation of NFκB and STAT3, functions as a local chemokine inducer, and acts as a mechanism for local inflammation, particularly chronic ones like rheumatoid arthritis and a multiple sclerosis. Moreover, we have recently shown that hyper activation of the IL-6 amplifier via regional neural activation establishes a gateway for immune cells including autoreactive T cells to pass the blood-brain barrier at dorsal vessels in 5(th) lumbar cord. Here we review how the IL-6 amplifier is activated by neural activation and the physiological relevance of the gateway to the central nervous system. Accumulating evidences continues to suggest that the IL-6 amplifier offers a potential molecular mechanism for the relationship between neural activation and the development of inflammatory diseases, which could establish a new interdisciplinary field that fuses neurology and immunology.


IL-6; inflammatory diseases; neural activation

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