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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v35.i5.20
pages 365-378

Role of Inflammation Amplifier-Induced Growth Factor Expression in the Development of Inflammatory Diseases

Ikuma Nakagawa
Division of Molecular Neuroimmunology, Institute for Genetic Medicine and Graduate School of Medicine Hokkaido University
Daisuke Kamimura
Division of Molecular Neuroimmunology, Institute for Genetic Medicine and Graduate School of Medicine Hokkaido University
Toru Atsumi
Division of Molecular Neuroimmunology, Institute for Genetic Medicine and Graduate School of Medicine Hokkaido University
Yasunobu Arima
Division of Molecular Neuroimmunology, Institute for Genetic Medicine and Graduate School of Medicine Hokkaido University
Masaaki Murakami
Division of Molecular Neuroimmunology, Institute for Genetic Medicine and Graduate School of Medicine Hokkaido University

ABSTRACT

Inflammation is a fundamental response induced by the immune system to protect the body against pathogens, tissue damage, and stress. At the same time, recent studies have suggested that chronically induced inflammation is involved in various human diseases and disorders. Thus, understanding the molecular mechanisms of chronic inflammation could provide therapeutic value. Many mediators such as cytokines or chemokines regulate inflammatory responses. Among them, interleukin(IL)-6 is a prominent cytokine that induces and maintains inflammatory reactions. It is expressed by activated CD4+ T cells and also non-immune cells such as fibroblasts and epithelial cells. We discovered an inflammation-induction machinery, the inflammation amplifier, which is activated by the simultaneous stimulation of nuclear factor-kappa B (NF-κB) and signal transducers and activator of transcription 3 (STAT3) via various cytokines like IL-17 and IL-6 in non-immune cells. Activation of the inflammation amplifier induces a synergistic increase of IL-6, inflammatory chemokines, and growth factors. Using genome-wide screening, we identified several growth factors as mediators of the inflammation amplifier. In this review, we highlight the role of growth factors in the inflammation mechanism with special attention on the inflammation amplifier.


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