Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adverse environmental conditions found in the periodontium during periodontitis pathogenesis stimulate local autophagy responses, mainly due to a continuous inflammatory response against the dysbiotic subgingival microbiome. The junctional epithelium represents the main site of the initial interaction between the host and the dysbiotic biofilm. Here, we investigated the role of autophagy in junctional epithelium keratinocytes (JEKs) in response to Aggregatibacter actinomycetemcomitans or its purified lipopolysaccharides (LPS). Immunofluorescence confocal analysis revealed an extensive nuclear translocation of transcription factor EB (TFEB) and consequently, an increase in autophagy markers and LC3-turnover assessed by immunoblotting and qRT-PCR. Correspondingly, challenged JEKs showed a punctuate cytosolic profile of LC3 protein contrasting with the diffuse distribution observed in untreated controls. Three-dimensional reconstructions of confocal images displayed a close association between intracellular bacteria and LC3-positive vesicles. Similarly, a close association between autophagic vesicles and the protein p62 was observed in challenged JEKs, indicating that p62 is the main adapter protein recruited during A. actinomycetemcomitans infection. Finally, the pharmacological inhibition of autophagy significantly increased the number of bacteria-infected cells as well as their death, similar to treatment with LPS. Our results indicate that A. actinomycetemcomitans infection induces autophagy in JEKs, and this homeostatic process has a cytoprotective effect on the host cells during the early stages of infection.
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PMID:Aggregatibacter Actinomycetemcomitans Induces Autophagy in Human Junctional Epithelium Keratinocytes. 3242 42

Rheumatoid arthritis (RA) and periodontitis share many epidemiological and pathological features, with emerging studies reporting a relationship between the two diseases. Recently, RA and periodontitis have been associated with autophagy. In the present study, we investigated the effects of cathepsin K (CtsK) inhibition on RA with periodontitis in a mouse model and its immunological function affecting autophagy. To topically inhibit CtsK periodontitis with arthritis in the animal model, adeno-associated virus (AAV) transfection was performed in periodontal and knee joint regions. Transfection of small interfering RNA (siRNA) was performed to inhibit CtsK in RAW264.7 cells. The effects of CtsK inhibition on the autophagy pathway were then evaluated in both in vivo and in vitro experiments. RA and periodontitis aggravated destruction and inflammation in their respective lesion areas. Inhibition of CtsK had multiple effects: (i) reduced destruction of alveolar bone and articular tissue, (ii) decreased macrophage numbers and inflammatory cytokine expression in the synovium, and (iii) alleviated expression of the autophagy-related transcription factor EB (TFEB) and microtubule-associated protein 1A/1B-light chain 3 (LC3) at the protein level in knee joints. Inhibition of CtsK in vitro reduced the expression of autophagy-related proteins and related inflammatory factors. Our data revealed that the inhibition of CtsK resisted the destruction of articular tissues and relieved inflammation from RA with periodontitis. Furthermore, CtsK was implicated as an imperative regulator of the autophagy pathway in RA and macrophages.
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PMID:Inhibition of Cathepsin K Alleviates Autophagy-Related Inflammation in Periodontitis-Aggravating Arthritis. 3290 Aug 14