Specific cytokines of interleukin-6 family interact with S100 proteins

Abstract

Cytokines of interleukin-6 (IL-6) family are important signaling proteins involved in various physiological and pathological processes. Earlier, we described interactions between IL-11 and S100P/B proteins from the family of S100 proteins engaged in the pathogenesis of numerous diseases. We probed here interactions between seven IL-6 family cytokines (IL-6, IL-11, OSM, LIF, CNTF, CT-1, and CLCF1) and fourteen S100 proteins (S100A1/A4/A6/A7/A8/A9/A10/A11/A12/A13/A14/A15/B/P). Surface plasmon resonance spectroscopy revealed formation of calcium-dependent complexes between IL-11, OSM, CNTF, CT-1, and CLCF1 and distinct subsets of S100A1/A6/B/P proteins with equilibrium dissociation constants of 19 nM - 12 µM. The existence of a network of interactions between Ca²⁺-loaded S100 proteins and IL-6 family cytokines suggest regulation of these cytokines by the extracellular forms of S100 proteins.

Keywords: CLCF1; CNTF; COPD; CT-1; IBD; IL-11; IL-6; JAK; Janus kinase; LIF; OSM; RU; SARS-CoV-2; SPR; STAT; cardiotrophin-1; cardiotrophin-like cytokine factor 1; chronic obstructive pulmonary disease; ciliary neurotrophic factor; gp130; inflammatory bowel disease; interleukin-11; interleukin-6; leukemia inhibitory factor; membrane glycoprotein 130; oncostatin-M; resonance unit; severe acute respiratory syndrome coronavirus-2; signal transducer and activator of transcription; surface plasmon resonance.