title: Alpha-MSH reduces the internalization of Staphylococcus aureus and down-regulates HSP 70, integrins and cytokine expression in human keratinocyte cell lines.
abstract: Alpha-melanocyte-stimulating hormone (alpha-MSH) is a neuropeptide predominantly produced by the pituitary gland, but it is also generated by many extra-pituitary cells including keratinocytes of the skin. This neuropeptide has anti-inflammatory and antimicrobial effects and probably contributes in innate immunity. Staphylococcus aureus is the aetiological agent of a wide range of infections in humans. Colonization of human skin by S. aureus is a characteristic feature of several skin diseases and is often followed by tissue invasion and severe cell damage. The aim of our study was to detect a possible role of alpha-MSH during the early infection stages in the adhesion and penetration of keratinocytes before cell damage. Our data demonstrated that alpha-MSH precociously down-regulates the production of integrins such as beta1 and heat shock surface protein 70, essential molecules for the entry of S. aureus. Moreover, in our experimental model, alpha-MSH induces the down-regulation of the pro-inflammatory cytokine expression and of the adhesion molecules in keratinocytes activated by S. aureus. Our data suggest that alpha-MSH plays a protective role in the skin by reducing infection and the inflammatory process.
authors.affiliation: Department of Experimental Medicine, Microbiology and Clinical Microbiology, Faculty of Medicine and Surgery, Second University of Naples, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Donnarumma
authors.forename: Iole
authors.initials: I
authors.lastname: Paoletti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Buommino
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Tufano
authors.forename: Adone
authors.initials: A
authors.lastname: Baroni
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation; D016023:Integrins / Q000096:biosynthesis*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012871:Skin Diseases / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000521:alpha-MSH / Q000502:physiology*
chemical_list: D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D016023:Integrins; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000521:alpha-MSH