The S100 Protein Family as Players and Therapeutic Targets in Pulmonary Diseases

Figure 1

Extracellular functions of S100 proteins. Several factors can trigger S100 proteins to be released or secreted from multiple cell types, including granulocytes. The extracellular S100 proteins interact with several pattern recognition receptors, resulting in proinflammatory signaling pathways that promote cell differentiation, inflammation, migration, apoptosis, proliferation, tissue repair, and a robust type-1 interferon response. Only a portion of the RAGE, HSPG/GPCR, TLR4, and CD147 responses are shown here. RAGE: receptor for advanced glycosylation end products; EGFR: epidermal growth factor receptor; ErbB: v-erb-b2 avian erythroblastic leukemia viral oncogene homolog; HSPG: heparan sulfate proteoglycans; GPCR: Gα9-coupled receptor; TLR4: toll-like receptor 4; SR: scavenger receptor; FGFR1: fibroblast growth factor receptor 1; CD147: cluster of differentiation 147; EMMPRIN: extracellular matrix metalloproteinase inducer; TIRAP: TIR domain containing adaptor protein; MyD88: myeloid differentiation factor 88; IRAK: interleukin 1 receptor-associated kinase; TAK1: transforming growth factor-β- (TGFβ-) activated kinase 1; TRIF: TIR-domain-containing adaptor protein inducing IFNβ; TRAM: translocating chain-associated membrane; TRAF: TNF receptor-associated factor; PI3K: phosphoinositide 3-kinases; Akt: protein kinase B; JNK: JUN N-terminal kinase; ERK: extracellular signal-regulated kinase; AP-1: activator protein 1; CREB1: cAMP-responsive element-binding protein 1; NF-κB: nuclear factor-κB; IRF: interferon regulatory factor; IκBα: nuclear factor of kappa light polypeptide gene enhancer in B cell inhibitor, alpha; IKK: inhibitor of NF-κB kinase.