title: Peptides from Paracoccidioides brasiliensis GP43 inhibit macrophage functions and inflammatory response.
abstract: Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis (Pb), a thermal dimorphic fungus. Its major antigen is a 43-kDa glycoprotein. Gp43 embodies different functions: it participates in evasion mechanisms during the installation of primary infection, stimulates granuloma-like formation in vitro and presents T-cell epitopes that induce protective response against the fungus. Here, we investigated epitopes from gp43 inhibitory of both, macrophage functions and inflammatory reaction. Different gp43 peptides, spanning the entire sequence of the molecule, were added to cultures of bone marrow-derived macrophages. After challenge with zymosan or Pb cells, phagocytic indexes were measured. Peptides expressed on the molecule surface were determined by graphic analysis using the Protean module; DNAstar Inc. Two peptides which decreased phagocytic index and were expressed at the surface of the molecule, P4 and P23, were selected for further studies. It was shown that both inhibited the release of NO by zymosan stimulated macrophages while enhanced release of H(2)O(2). The release of TNF-alpha in culture supernatants from in vitro phagocytic tests showed different response depending of P4 concentration (data not shown). In vivo assays with Mycobacterium bovis - bacillus Calmette-Guérin (BCG) or Pb cells demonstrated that these peptides presented non-specific and specific anti-inflammatory properties.
authors.affiliation: Universidade Federal de São Paulo - UNIFESP, Department of Microbiology, Immunology and Parasitology, Discipline of Immunology, São Paulo, Brazil.
authors.forename: Adriana Y C
authors.initials: AY
authors.lastname: Konno
authors.forename: Juliana T
authors.initials: JT
authors.lastname: Maricato
authors.forename: Fabiana T C
authors.initials: FT
authors.lastname: Konno
authors.forename: Mário
authors.initials: M
authors.lastname: Mariano
authors.forename: José Daniel
authors.initials: JD
authors.lastname: Lopes
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000737:chemistry* / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005656:Fungal Proteins / Q000737:chemistry* / Q000494:pharmacology; D006023:Glycoproteins / Q000737:chemistry* / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides / Q000737:chemistry / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000382:microbiology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects
chemical_list: C103180:43 kDa protein, Paracoccidioides; D000946:Antigens, Fungal; D005656:Fungal Proteins; D006023:Glycoproteins; D010455:Peptides