S100A proteins as molecular targets in the ocular surface inflammatory diseases

Abstract

The S100 proteins are calcium-binding proteins that are exclusively expressed in vertebrates, where they interact with enzymes, cytoskeletal proteins, receptors, transcription factors, and nucleic acids to regulate proliferation, differentiation, apoptosis, inflammation, cell migration, energy metabolism, and Ca(2+) homeostasis. In this review, we focus on the S100A8 and S100A9 members of the family that are involved in the regulation of neutrophil chemotaxis and inflammation related to ocular surface diseases such as dry eye, meibomian gland dysfunction, pterygium, and corneal neovascularization. In our previous studies, we have found that the levels of S100A8 and S100A9 were elevated in these inflammatory ocular diseases. For instance, S100A8 and A9 were found to be upregulated in pterygium tissues at both transcript and protein levels. These findings are consistent with the role of S100A8 and S100A9 proteins in activating the innate immune system in the eye via Toll-like receptors (TLRs) and altering the immune tolerance of the eye-associated lymphoid system. Recently, use of S100A8-targeting antibody has shown promising results in targeting corneal neovascularization. Injection of S100A8 has been shown to inhibit eosinophilic infiltration and thus may have potential therapeutic implications in allergic diseases.

Keywords: CB-CorNV; CK; Chemical burn-induced corneal neovascularization; Cytokeratin; HNP; Human neutrophil peptide; IL; Interleukin; Isobaric tagging for relative and absolute quantification; MAPK; MGD; MIP-2; MMPs; Macrophage inflammatory protein 2; Matrix metalloproteinases; Meibomian gland dysfunction; Mitogen-activated protein kinase; NFκ; Nuclear factor kappa; ORM1; PIP; Prolactin-inducible protein; RAGE; ROS; Reactive oxygen species; Receptor for advanced glycation endproducts; S-CorNV; S100A proteins; SCC; SELDI-TOF-MS; Squamous cell carcinoma; Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry; Suture-induced corneal neovascularization; TIRAP; TLR; TNF-α; Toll-interleukin 1 receptor domain-containing adaptor protein; Toll-like receptor; Tumor necrosis factor-α; UV; Ultraviolet; VEGF; Vascular endothelial growth factor; corneal angiogenesis; dry eye; iTRAQ; meibomian gland disease; meibomian gland dysfunction; ocular surface; pterygium; α1-acid glycoprotein 1.