Extracellular vesicles of P. gingivalis-infected macrophages induce lung injury

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1867

Article

Yoshida, Kayo¹  Yoshida, Kaya²  Fujiwara, Natsumi¹  Seyama, Mariko¹  Ono, Kisho³  Kawai, Hotaka⁴  Guo, Jiajie^5,6  Wang, Ziyi⁷  Weng, Yao⁶  Yu, Yaqiong^5,6  Uchida-Fukuhara, Yoko⁶  Ikegame, Mika⁶  Sasaki, Akira³  Nagatsuka, Hitoshi⁴  Kamioka, Hiroshi⁷  Okamura, Hirohiko⁶  Ozaki, Kazumi¹ 

[1] Tokushima Univ, Inst Biomed Sci, Dept Oral Healthcare Promot, Grad Sch, Tokushima, Japan

[2] Tokushima Univ, Inst Biomed Sci, Dept Oral Healthcare Educ, Grad Sch, Tokushima, Japan

[3] Grad Sch Med, Dept Oral & Maxillofacial Surg & Biopathol, Okayama, Japan

[4] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral Pathol & Med, Okayama, Japan

[5] China Med Univ, Sch & Hosp Stomatol, Liaoning Prov Key Lab Oral Dis, Shenyang, Peoples R China

[6] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral Morphol, Okayama, Japan

[7] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthodont, Okayama, Japan

关键词: Periodontal diseases;    Lung diseases;    Infection;    Inflammation;    Epithelial cells;    Animal experimentation;   

DOI  :  10.1016/j.bbadis.2021.166236

来源: Elsevier

【 摘 要 】

Periodontal diseases are common inflammatory diseases that are induced by infection with periodontal bacteria such as Porphyromonas gingivalis (Pg). The association between periodontal diseases and many types of systemic diseases has been demonstrated; the term periodontal medicine is used to describe how periodontal infection/ inflammation may impact extraoral health. However, the molecular mechanisms by which the factors produced in the oral cavity reach multiple distant organs and impact general health have not been elucidated. Extracellular vesicles (EVs) are nano-sized spherical structures secreted by various types of cells into the tissue microenvironment, and influence pathophysiological conditions by delivering their cargo. However, a detailed understanding of the effect of EVs on periodontal medicine is lacking. In this study, we investigated whether EVs derived from Pg-infected macrophages reach distant organs in mice and influence the pathophysiological status. EVs were isolated from human macrophages, THP-1 cells, infected with Pg. We observed that EVs from Pg-infected THP-1 cells (Pg-inf EVs) contained abundant core histone proteins such as histone H3 and translocated to the lungs, liver, and kidneys of mice. Pg-inf EVs also induced pulmonary injury, including edema, vascular congestion, inflammation, and collagen deposition causing alveoli destruction. The Pg-inf EVs or the recombinant histone H3 activated the NF-.B pathway, leading to increase in the levels of pro-inflammatory cytokines in human lung epithelial A549 cells. Our results suggest a possible mechanism by which EVs produced in periodontal diseases contribute to the progression of periodontal medicine.

【 授权许可】

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