Effector Pathways of Toll-like Receptor-inducible Innate Immune Responses in Macrophages

Toll-like receptors (TLR) are well-characterized pattern recognition receptors that can recognize and respond to diverse pathogen-associated or danger-associated molecular patterns during infection. TLR signaling in macrophages triggers in the intracellular signaling pathways through the recruitment of various adaptor and signaling proteins, and results in the activation of effector mechanisms and pathways that are important for host defense to intracellular bacteria. Effector mechanisms include inflammatory responses, cytokine generation, production of reactive oxygen species, and antimicrobial proteins. Accumulating studies showed that autophagy is a key pathway in the maintenance of homeostasis and housekeeping functions during infection and inflammation. In this review, we summarize the major effector pathways and mechanisms in the activation of TLR-inducible innate immune responses in macrophages. In addition, we focus the emerging evidence of crosstalk between autophagy and TLR-mediated signaling in terms of effector function of innate immune responses. A better understanding of effector functions by the activation of TLR-mediated signaling cascades contributes to the development of new therapeutics and vaccines against various intracellular pathogenic infections.

A Research Progress on the Antimicrobial Proteins of Ginseng / 世界科学技术-中医药现代化

Panax ginseng is a precious medicinal herb both in China and abroad with high medicinal and economic value.Ginseng disease has been recognized as the main factor restricting its application.Modern molecular biology for the disease resistance of ginseng promoted the development of new methods.In this study,it was found that the antimicrobial proteins of ginseng involved lipid transfer protein,cyclophilin,defensins,PR-4 and PR-10,showing inhibitory effects on various pathogens.These findings provided a reference for the control of ginseng diseases.

Antimicrobial Proteins in Intestine and Inflammatory Bowel Diseases

Mucosal surface of the intestinal tract is continuously exposed to a large number of microorganisms. To manage the substantial microbial exposure, epithelial surfaces produce a diverse arsenal of antimicrobial proteins (AMPs) that directly kill or inhibit the growth of microorganisms. Thus, AMPs are important components of innate immunity in the gut mucosa. They are frequently expressed in response to colonic inflammation and infection. Expression of many AMPs, including human beta-defensin 2-4 and cathelicidin, is induced in response to invasion of pathogens or enteric microbiota into the mucosal barrier. In contrast, some AMPs, including human alpha-defensin 5-6 and human beta-defensin 1, are constitutively expressed without microbial contact or invasion. In addition, specific AMPs are reported to be associated with inflammatory bowel disease (IBD) due to altered expression of AMPs or development of autoantibodies against AMPs. The advanced knowledge for AMPs expression in IBD can lead to its potential use as biomarkers for disease activity. Although the administration of exogenous AMPs as therapeutic strategies against IBD is still at an early stage of development, augmented induction of endogenous AMPs may be another interesting future research direction for the protective and therapeutic purposes. This review discusses new advances in our understanding of how intestinal AMPs protect against pathogens and contribute to pathophysiology of IBD.

Anti-adenoviral Effects of Human Cationic Antimicrobial Protein-18/LL-37, an Antimicrobial Peptide, by Quantitative Polymerase Chain Reaction

PURPOSE: Antimicrobial peptides have an important role in self-protection of the ocular surface. Human cationic antimicrobial protein (hCAP)-18 is a linear, alpha-helical peptide that consists of a conserved pro-sequence called a cathelin-like domain and a C-terminal peptide named LL-37. We investigated the in vitro anti-adenoviral activity of hCAP-18/LL-37 in several adenovirus types, inducing keratoconjunctivitis. METHODS: A549 cells were used for viral cell culture, and human adenovirus (HAdV) types 3 (HAdV3, species B), 4 (species E), 8, 19a, and 37 (species D) were used. The cytotoxicity of LL-37 was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay to obtain 50% cytotoxic concentration. After pretreatment of A549 cells with serial dilutions of LL-37 for 24 hours, adenovirus was cultured for seven days, and adenoviral DNA was quantitatively measured by real-time polymerase chain reaction (PCR). RESULTS: The 50% effective concentration of LL-37 obtained by real-time PCR ranged between 118 and 270 microM. LL-37 showed a significant inhibitory effect on adenoviral proliferation in all adenovirus types except HAdV4 in a dose-dependent manner. CONCLUSIONS: LL-37 has significant inhibitory activity against HAdV3, 8, and 19, which induce keratoconjunctivitis. These results indicate that hCAP-18/LL-37 may be a possible candidate for the treatment of HAdV keratoconjunctivitis.

A novel antifungal protein from seeds of Sesbania virgata (Cav.) Pers. (Leguminosae-Faboideae) / Uma nova proteína antifúngica obtida de sementes de Sesbania virgata (Cav.) Pers. (Leguminosae-Faboideae)

A novel antifungal protein with a molecular mass around 50 kDa was purified from seeds of Sesbania virgata (Cav.) Pers. using ammonium sulfate fractionation followed by gel filtration on a Sephadex G-75 Superfine (Sigma) column and reverse-phase high performance liquid chromatography on a C8 column. The protein, designated FP1-A, with a novel N-terminal sequence AMVHSPGG(S)FS(P), showed growth inhibitory activity of filamentous fungi Aspergillus niger, Cladosporium cladosporioides, Colletotrichum gloeosporioides and Fusarium solani.

Uma nova proteína com atividade antifúngica, com massa molar de cerca de 50 kDa, foi purificada de sementes de Sesbania virgata (Cav.) Pers. utilizando precipitação com sulfato de amônia, filtração em gel em coluna de Sephadex G-75 Superfine (Sigma) e cromatografia líquida de alta eficiência em fase reversa (coluna C8). A proteína purificada foi designada FP1-A, com a sequência N-terminal AMVHSPGG(S)FS(P), apresentando atividade inibitória do crescimento dos fungos filamentosos Aspergillus niger, Cladosporium cladosporioides, Colletotrichum gloeosporioides e Fusarium solani.