title: Do reciprocal interactions between cell stress proteins and cytokines create a new intra-/extra-cellular signalling nexus?
abstract: Cytokine biology began in the 1950s, and by 1988, a large number of cytokines, with a myriad of biological actions, had been discovered. In 1988, the basis of the protein chaperoning function of the heat shock, or cell stress, proteins was identified, and it was assumed that this was their major activity. However, since this time, evidence has accumulated to show that cell stress proteins are secreted by cells and can stimulate cellular cytokine synthesis with the generation of pro- and/or anti-inflammatory cytokine networks. Cell stress can also control cytokine synthesis, and cytokines are able to induce, or even inhibit, the synthesis of selected cell stress proteins and may also promote their release. How cell stress proteins control the formation of cytokines is not understood and how cytokines control cell stress protein synthesis depends on the cellular compartment experiencing stress, with cytoplasmic heat shock factor 1 (HSF1) having a variety of actions on cytokine gene transcription. The endoplasmic reticulum unfolded protein response also exhibits a complex set of behaviours in terms of control of cytokine synthesis. In addition, individual intracellular cell stress proteins, such as Hsp27 and Hsp90, have major roles in controlling cellular responses to cytokines and in controlling cytokine synthesis in response to exogenous factors. While still confusing, the literature supports the hypothesis that cell stress proteins and cytokines may generate complex intra- and extra-cellular networks, which function in the control of cells to external and internal stressors and suggests the cell stress response as a key parameter in cytokine network generation and, as a consequence, in control of immunity.
authors.affiliation: Department of Microbial Diseases, Eastman Dental Institute, University College London, London, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Henderson
authors.forename: Frank
authors.initials: F
authors.lastname: Kaiser
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D016207:Cytokines; D006360:Heat-Shock Proteins