Regulation of cytokine signaling and inflammation.
Inflammation progresses by the action of pro-inflammatory cytokines, including interleukin-1 (IL-1), the tumor necrosis factor (TNF), gamma-interferon (IFNgamma), IL-12, IL-18, and the granulocyte-macrophage colony-stimulating factor, and is resolved by anti-inflammatory cytokines such as IL-4, IL-10, IL-13, IFNalpha, and the transforming growth factor (TGF)beta. The intracellular signal transduction pathways of these cytokines have been studied extensively, and these pathways ultimately activate transcription factors, such as NF-kappaB, Smad, and STATs. Recently, the negative-feedback regulation of these pathways has been identified. In this review, we provide examples of the relationship between cytokine signal transduction, negative-signal regulation, and inflammatory disease models. Furthermore, we illustrate several approaches for treating inflammatory diseases by modulating extracellular and intracellular signaling pathways.
Hanada
Toshitkatsu
T
Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Yoshimura
Akihiko
A
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D020672:I-kappa B Proteins / Q000502:physiology; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology*; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D016328:NF-kappa B / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D018121:Receptors, Cytokine / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
D016207:Cytokines; D004268:DNA-Binding Proteins; D006133:Growth Substances; D020672:I-kappa B Proteins; D016328:NF-kappa B; D018121:Receptors, Cytokine; D012097:Repressor Proteins; D051785:Smad Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D011494:Protein Kinases