| First Author | Sakaguchi M | Year | 2016 |
| Journal | J Invest Dermatol | Volume | 136 |
| Issue | 11 | Pages | 2240-2250 |
| PubMed ID | 27388991 | Mgi Jnum | J:238126 |
| Mgi Id | MGI:5818373 | Doi | 10.1016/j.jid.2016.06.617 |
| Citation | Sakaguchi M, et al. (2016) Identification of an S100A8 Receptor Neuroplastin-beta and its Heterodimer Formation with EMMPRIN. J Invest Dermatol 136(11):2240-2250 |
| abstractText | We previously reported a positive feedback loop between S100A8/A9 and proinflammatory cytokines mediated by extracellular matrix metalloproteinase inducer, an S100A9 receptor. Here, we identify neuroplastin-beta as an unreported S100A8 receptor. Neuroplastin-beta and extracellular matrix metalloproteinase inducer form homodimers and a heterodimer, and they are co-localized on the surface of cultured normal human keratinocytes. Knockdown of both receptors suppressed cell proliferation and proinflammatory cytokine induction. Upon stimulation with S100A8, neuroplastin-beta recruited GRB2 and activated extracellular signal-regulated kinase, resulting in keratinocyte proliferation. Keratinocyte proliferation in response to inflammatory stimuli was accelerated in involucrin promoter-driven S100A8 transgenic mice. Further, S100A8 and S100A9 were strongly up-regulated and co-localized in lesional skin of atopic dermatitis patients. Our results indicate that neuroplastin-beta and extracellular matrix metalloproteinase inducer form a functional heterodimeric receptor for S100A8/A9 heterodimer, followed by recruitment of specific adaptor molecules GRB2 and TRAF2, and this signaling pathway is involved in activation of both keratinocyte proliferation and skin inflammation in atopic skin. Suppression of this pathway might have potential for treatment of skin diseases associated with chronic inflammation such as atopic dermatitis. |
