Second messenger systems in the regulation of cytokines and adhesion molecules in the central nervous system.
Cytokines are a group of secreted proteins that exhibit diverse biological activity and are especially important in immune and inflammatory responses. The inappropriate production of cytokines in the central nervous system (CNS) has been implicated in a number of disease states such as Alzheimer's disease, multiple sclerosis, and AIDS dementia complex. This article focuses on the biological role of three cytokines in the CNS, interleukin-6 (IL-6), tumor necrosis factor alpha, and nerve growth factor, with an emphasis on production by glial cells. We will discuss the diverse intracellular signaling pathways that regulate expression of these cytokines by glial cells and then describe the second messenger systems that mediate cytokine-induced responses in the CNS, with an emphasis on adhesion molecule expression. We conclude by discussing the complexities of signal transduction pathways, particularly "cross-talk" between different intracellular mediators.
Department of Cell Biology, University of Alabama at Birmingham, Alabama 35294-0005, USA.
E N
EN
Benveniste
B S
BS
Huneycutt
P
P
Shrikant
M E
ME
Ballestas
D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D017628:Microglia / Q000378:metabolism; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D015815:Cell Adhesion Molecules; D016207:Cytokines; D015850:Interleukin-6; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C