RESUMEN
In periodontitis, a common chronic inflammatory condition, gram-negative-rich bacterial biofilms trigger, in susceptible individuals, perpetuating inflammation that results in extensive tissue damage of tooth supporting structures. To delineate immune cell-dependent mechanisms whereby bacterial challenge drives persistent destructive inflammation in periodontitis and other inflammatory diseases, we studied involved tissues ex vivo and investigated host cell responses to the periodontal pathogen Porphyromonas gingivalis, in vitro. Diseased lesions were populated by abundant Th17 cells, linked to infection, chronic inflammation/autoimmunity and tissue pathology. In vitro, P. gingivalis, particularly the more virulent strain W83, stimulated myeloid antigen presenting cells (APC) to drive Th17 polarization. Supernatants from myeloid APC exposed to P. gingivalis were capable of enhancing Th17 but not Th1 polarization. P. gingivalis favored the generation of Th17 responses by stimulating the production of Th17 related cytokines IL-1ß, IL-6 and IL-23, but not Th1 related IL-12. By inducing NFκB activation, P. gingivalis promoted IL-1ß, IL-6 and IL-12p40 production, but not IRF3 phosphorylation, connected to generation of the IL-12p35 chain, ultimately restricting formation of the intact IL-12 molecule. Promotion of Th17 lineage responses was also aided by P. gingivalis proteases, which appeared to differentially degrade pivotal cytokines. In this regard, IL-12 was largely degraded by P. gingivalis, whereas IL-1ß was more resistant to proteolysis. Our data unveil multiple pathways by which P. gingivalis may orchestrate chronic inflammation, providing insights into interventional strategies.
Asunto(s)
Infecciones por Bacteroidaceae/inmunología , Periodontitis Crónica/inmunología , Interacciones Huésped-Patógeno , Porphyromonas gingivalis/inmunología , Células Th17/inmunología , Células Presentadoras de Antígenos/metabolismo , Células Presentadoras de Antígenos/microbiología , Infecciones por Bacteroidaceae/microbiología , Células Cultivadas , Periodontitis Crónica/microbiología , Medios de Cultivo Condicionados/farmacología , Humanos , Inflamación/inmunología , Inflamación/microbiología , Factor 3 Regulador del Interferón/genética , Factor 3 Regulador del Interferón/inmunología , Subunidad p35 de la Interleucina-12/inmunología , Subunidad p35 de la Interleucina-12/metabolismo , Subunidad p40 de la Interleucina-12/inmunología , Subunidad p40 de la Interleucina-12/metabolismo , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo , Interleucina-23/inmunología , Interleucina-23/metabolismo , Interleucina-6/inmunología , Interleucina-6/metabolismo , Células Mieloides/metabolismo , Células Mieloides/microbiología , FN-kappa B/genética , FN-kappa B/inmunología , Fosforilación , Proteolisis , Transducción de Señal , Células Th17/efectos de los fármacos , Células Th17/metabolismoRESUMEN
A novel method utilizing microbial treatment for cleaner production of diosgenin from Dioscorea zingiberensis C.H. Wright (DZW) was presented. A new Bacillus pumilus HR19, which has the great ability to secrete pectinase, was screened and applied in the microbial treatment. Low-pressure steam expansion pretreatment (LSEP) was employed in advance to assist microbial treatment efficiently in releasing saponins, which are the precursors of diosgenin. Compared with the traditional process of acid hydrolysis, this novel process reduced the consumptions of water, acid and organic solvent by more than 92.5%, 97.0%, 97.0%, respectively, while simultaneously increasing the diosgenin yield by 6.21%. In addition, the microbial treatment was more efficient than enzymatic treatment, which arised from that microorganisms could be induced to secrete related enzymes by the compositions of DZW and relieve product inhibition by utilizing enzyme hydrolysates.