PMID- 19026760 OWN - NLM STAT- MEDLINE DCOM- 20090505 LR - 20161020 IS - 1286-4579 (Print) IS - 1286-4579 (Linking) VI - 11 IP - 1 DP - 2009 Jan TI - Peptides from Paracoccidioides brasiliensis GP43 inhibit macrophage functions and inflammatory response. PG - 92-9 LID - 10.1016/j.micinf.2008.10.011 [doi] AB - 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-Guerin (BCG) or Pb cells demonstrated that these peptides presented non-specific and specific anti-inflammatory properties. FAU - Konno, Adriana Y C AU - Konno AY AD - Universidade Federal de Sao Paulo - UNIFESP, Department of Microbiology, Immunology and Parasitology, Discipline of Immunology, Sao Paulo, Brazil. FAU - Maricato, Juliana T AU - Maricato JT FAU - Konno, Fabiana T C AU - Konno FT FAU - Mariano, Mario AU - Mariano M FAU - Lopes, Jose Daniel AU - Lopes JD LA - eng PT - Journal Article DEP - 20081106 PL - France TA - Microbes Infect JT - Microbes and infection JID - 100883508 RN - 0 (43 kDa protein, Paracoccidioides) RN - 0 (Antigens, Fungal) RN - 0 (Fungal Proteins) RN - 0 (Glycoproteins) RN - 0 (Peptides) SB - IM MH - Animals MH - Antigens, Fungal/*chemistry/pharmacology MH - Cells, Cultured MH - Female MH - Fungal Proteins/*chemistry/pharmacology MH - Glycoproteins/*chemistry/pharmacology MH - Inflammation/drug therapy MH - Macrophages/*drug effects/immunology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Paracoccidioides/chemistry/*immunology MH - Paracoccidioidomycosis/microbiology MH - Peptides/chemical synthesis/chemistry/*pharmacology MH - Phagocytosis/drug effects EDAT- 2008/11/26 09:00 MHDA- 2009/05/06 09:00 CRDT- 2008/11/26 09:00 PHST- 2008/10/09 00:00 [received] PHST- 2008/10/20 00:00 [accepted] PHST- 2008/11/26 09:00 [pubmed] PHST- 2009/05/06 09:00 [medline] PHST- 2008/11/26 09:00 [entrez] AID - S1286-4579(08)00303-1 [pii] AID - 10.1016/j.micinf.2008.10.011 [doi] PST - ppublish SO - Microbes Infect. 2009 Jan;11(1):92-9. doi: 10.1016/j.micinf.2008.10.011. Epub 2008 Nov 6.