Carl D. Richards, Rohan Gandhi, Fernando Botelho, Lilian Ho, John F. Paolini
DOI: 10.2340/00015555-3505

To evaluate cellular response to oncostatin M (OSM) in comparison to interleukin (IL)-31, we analyzed monocyte chemoattractant protein 1 (MCP-1) as a readout for OSM responses with and without IL-4, IL-13, anti-OSM receptor β monoclonal antibody KPL-716, and anti–IL-31 receptor α antibody in human epidermal keratinocytes and human dermal fibroblasts in vitro. In human epidermal keratinocytes, OSM significantly induced STAT3 or STAT1 phosphorylation and synergized with IL-13 or IL-4 in elevating MCP-1. In human dermal fibroblasts, OSM results were similar, and leukemia inhibitory factor or IL-31 minimally activated STAT3 but not MCP-1. OSM significantly stimulated mRNA for type II IL-4 receptor and type II OSM receptor. KPL-716, not anti–IL-31Rα, significantly attenuated MCP-1 response to OSM and OSM + IL-4 in human epidermal keratinocytes and human dermal fibroblasts. OSM, not leukemia inhibitory factor or IL-31, synergized with IL-4 and IL-13 in human epidermal keratinocytes and human dermal fibroblasts, suggesting therapeutic potential of KPL-716 in inflammatory dermatologic diseases distinct from IL-31 inhibition.

Oncostatin M, part of the gp130 cytokine family that includes leukemia inhibitory factor, interleukin-6, and interleukin-31, is involved in inflammation, epidermal integrity, and fibrosis. To elucidate the role of oncostatin M in inflammatory diseases, this work characterizes the response of human epidermal keratinocytes and human dermal fibroblasts to oncostatin M. Furthermore, this work characterizes the in vitro effect of KPL-716, a fully human monoclonal antibody that specifically targets the oncostatin M receptor β chain to simultaneously inhibit interleukin-31 and oncostatin M signaling, on oncostatin M-stimulated keratinocytes and fibroblasts. Results demonstrate therapeutic potential for KPL-716 via its oncostatin M signaling inhibitory effect that is distinct from its interleukin-31 inhibition.

Figure S1
Table SII
Table SIII
Table SIV
Table SV
Table SI