The soluble IL-6 receptors: serum levels and biological function.
IL-6 exerts its biological activities through interaction with specific receptors expressed on the surface of target cells. IL-6 binds first to a low-affinity (10(-9) M) subunit, a 80 kDa glycoprotein also called gp80 or IL-6R alpha. The IL-6/IL-6R alpha complex recruits the signal-transducing b subunit, a 130 kDa glycoprotein called gp130. The association of gp130 with IL-6 and IL-6R alpha leads to the formation of the high-affinity IL-6 receptor complex, to the linkage of two gp130 subunits and to signal transduction. Soluble forms of both receptors have been described and found in biological fluids. Soluble cytokine receptors are generated by either proteolytic cleavage of their membrane moiety or by alternative splicing. Both mechanisms have been described for sIL-6R and sgp130 formation. Interestingly, the association of IL-6 with the soluble form of IL-6R alpha is capable of eliciting a biological response in cells that express only the membrane gp130. This type of activation, called "trans-signalling", renders virtually all cells capable of responding to IL-6/sIL-6R alpha complexes, making for a large new spectrum of IL-6 activities, ranging from the control of the immune response to involvement in pathological states. In this review the biological activities of IL-6 will be considered in the light of new knowledge concerning the association of IL-6 and the soluble IL-6 receptors.
Montero-Julian
F A
FA
Immunotech (a Beckman-Coulter Company), Marseille, France. montero@immunotech.fr
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D050822:Cytokine Receptor gp130; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000502:physiology; D008969:Molecular Sequence Data; D019947:Receptors, Interleukin-6 / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D012995:Solubility
D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130