title: S100B induces the release of pro-inflammatory cytokines in alveolar type I-like cells.
abstract: S100B, a 21kDa cytosolic calcium-binding protein of the EF-hand type, present in high abundance in the brain, stimulates inflammatory responses in different cellular types inside and outside the central nervous system. Most of extracellular S100B effects are mediated by Receptor for Advanced Glycation End-products (RAGE). RAGE is highly expressed in lung by Alveolar Type-I (AT-I) cells and its activation contributes to ALI/ARDS pathogenesis. In this in-vitro study, we tested the hypothesis that S100B stimulates an ATI-derived cell line (R3/1) to secrete inflammatory mediators involved in lung inflammation. Our main result is that S100B stimulates R3/1 cells to secrete TNF-alpha and IL-6 (well-known pro-inflammatory cytokines in lung inflammation and neurogenic pulmonary edema), but not sICAM-1, CINC-1 or CINC-3. Soluble RAGE (sRAGE) reduced S100B-dependent secretion of TNF-alpha but did not decrease S100B-dependent secretion of IL-6. Moreover, in absence of S100B, sRAGE enhanced IL-6 release. This study demonstrates that in vitro S100B dose-dependently stimulated R3/1 cells, to enhance the secretion of TNF-alpha and IL-6; S100B pro-inflammatory activity might be mediated at least in part by RAGE. Besides acting as decoy receptor, sRAGE could have pro-inflammatory properties.
authors.affiliation: Dipartimento di Medicina, Anestesiologia e Rianimazione, University of Salerno, Salerno, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Piazza
authors.forename: E
authors.initials: E
authors.lastname: Leggiero
authors.forename: G
authors.initials: G
authors.lastname: De Benedictis
authors.forename: L
authors.initials: L
authors.lastname: Pastore
authors.forename: F
authors.initials: F
authors.lastname: Salvatore
authors.forename: R
authors.initials: R
authors.lastname: Tufano
authors.forename: E
authors.initials: E
authors.lastname: De Robertis
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D064568:S100 Calcium Binding Protein beta Subunit / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D014409:Tumor Necrosis Factor-alpha