title: The pathological and physiological roles of IL-6 amplifier activation.
abstract: 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.
authors.affiliation: Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, and WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan. murakami@molonc.med.osaka-u.ac.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
authors.forename: Toshio
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology*; D008159:Lumbar Vertebrae; D051379:Mice; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000473:pathology
chemical_list: D024042:Collagen Type I; D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse
keywords: IL-6; inflammatory diseases; neural activation