The protein LJM 111 from Lutzomyia longipalpis Salivary Gland Extract (SGE) accounts for the SGE-inhibitory effects upon inflammatory parameters in experimental arthritis model

• Published in: International immunopharmacology 2012-04, Vol.12 (4), p.603-610
• Main Authors: Grespan, Renata, Lemos, Henrique P., Carregaro, Vanessa, Verri, Waldiceu A., Souto, Fabricio O., de Oliveira, Carlo J.F., Teixeira, Clarissa, Ribeiro, José Marcos, Valenzuela, Jesus G., Cunha, Fernando Q.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Arthritis; Arthritis, Experimental - immunology; Biological and medical sciences; Cell Movement; Chemotaxis; Cytokines - immunology; Dendritic Cells - immunology; Diseases of the osteoarticular system; Female; G-Protein-Coupled Receptor Kinase 2 - immunology; Insect Proteins - pharmacology; LJM 111 protein; Lymph Nodes - cytology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Miscellaneous. Osteoarticular involvement in other diseases; Neutrophils - immunology; Ovalbumin - immunology; Pharmacology. Drug treatments; Psychodidae; Receptors, Interleukin-8B - immunology; Recombinant Proteins - pharmacology; Salivary gland extract; Salivary Glands - immunology; Salivary Proteins and Peptides - pharmacology; Serum Albumin, Bovine - immunology
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2012.02.004

Several studies have pointed out the immunomodulatory properties of the Salivary Gland Extract (SGE) from Lutzomyia longipalpis. We aimed to identify the SGE component (s) responsible for its effect on ovalbumin (OVA)-induced neutrophil migration (NM) and to evaluate the effect of SGE and components in the antigen-induced arthritis (AIA) model. We tested the anti-arthritic activities of SGE and the recombinant LJM111 salivary protein (rLJM111) by measuring the mechanical hypernociception and the NM into synovial cavity. Furthermore, we measured IL-17, TNF-α and IFN-γ released by lymph nodes cells stimulated with mBSA or anti-CD3 using enzyme-linked immunosorbent assay (ELISA). Additionally, we tested the effect of SGE and rLJM111 on co-stimulatory molecules expression (MHC-II and CD-86) by flow cytometry, TNF-α and IL-10 production (ELISA) of bone marrow-derived dendritic cells (BMDCs) stimulated with LPS, chemotaxis and actin polymerization from neutrophils. Besides, the effect of SGE on CXCR2 and GRK-2 expression on neutrophils was investigated. We identified one plasmid expressing the protein LJM111 that prevented NM in OVA-challenged immunized mice. Furthermore, both SGE and rLJM111 inhibited NM and pain sensitivity in AIA and reduced IL-17, TNF-α and IFN-γ. SGE and rLJM111 also reduced MHC-II and CD-86 expression and TNF-α whereas increased IL-10 release by LPS-stimulated BMDCs. SGE, but not LJM 111, inhibited neutrophils chemotaxis and actin polymerization. Additionally, SGE reduced neutrophil CXCR2 expression and increased GRK-2. Thus, rLJM111 is partially responsible for SGE mechanisms by diminishing DC function and maturation but not chemoattraction of neutrophils. ► The salivary gland extract (SGE) inhibits neutrophil chemotaxis in a GRK-dependent downregulation of CXCR2 expression. ► The SGE modulates dendritic cells function and maturation. ► The LJM 111 protein modulates dendritic cells function and maturation.