Identification of a novel IL-6 isoform binding to the endogenous IL-6 receptor

Publication

Identification of a novel IL-6 isoform binding to the endogenous IL-6 receptor

Journal Paper/Review - Jul 1, 2002

Bihl Michel P, Heinimann Karl, Rüdiger Jochen, Eickelberg Oliver, Perruchoud André P, Tamm Michael, Roth Michael

Citation

Bihl M, Heinimann K, Rüdiger J, Eickelberg O, Perruchoud A, Tamm M, Roth M. Identification of a novel IL-6 isoform binding to the endogenous IL-6 receptor. Am J Respir Cell Mol Biol 2002; 27:48-56.

Type

Journal Paper/Review (English)

Journal

Am J Respir Cell Mol Biol 2002; 27

Publication Date

Jul 1, 2002

Issn Print

1044-1549

Pages

48-56

Brief description/objective

Interleukin (IL)-6 is a multifunctional cytokine showing a wide variety of biologic functions on various tissues. Extracellular IL-6 signals through heterohexameric complex formation with IL-6 receptor-alpha (IL-6Ralpha) and IL-6 receptor-beta (IL-6Rbeta). In analogy to cytokines IL-2 and IL-4, we investigated the expression of IL-6 splice variants in lung tissue and cultivated fibroblasts. In human lung specimens, four different IL-6 transcripts were characterized as follows: native IL-6; IL-6 missing either exon 2 (IL-6Delta2), exon 4 (IL-6Delta4), or missing both; and exons 2 and 4 (IL-6Delta2,4). Only native IL-6 and IL-6Delta4 encoded for proteins of ~ 26 and 17 kD, respectively. Although the overall structure and most functional sites of the IL-6Delta4 protein were predicted to be maintained, IL-6Delta4 was found to lack two amino acids necessary for IL-6/IL-6 homodimerization as well as two of the six amino acids required for interaction with IL-6Rbeta. Receptor mobility shift assays confirmed that the new isoform formed a stable complex with IL-6Ralpha; however, no interaction with IL-6Rbeta was observed. Thus, IL-6Delta4 is likely to compete with native IL-6 for IL-6Ralpha binding but fails to transmit IL-6Rbeta-mediated signaling.