Page 110 - GPD-1-2

Gene & Protein in Disease Exosomes connect periodontitis and systemic diseases

the occurrence and development of periodontitis. When macrophages and other inflammatory cells homing into
bacteria invade in periodontal tissue, epithelial cells (ECs) damaged sites . In the current paper, we introduce
[44]
can act as a physical barrier against them, and elicit innate several common inflammatory factors. TNF-α, produced
[32]
and acquired immune responses . Neutrophils will be by macrophages, lymphocytes, and natural killer cells, is
recruited and release lysosomal enzymes to kill bacteria, but a cytokine with extensive biological effects, can initiate
[45]
they also can damage the surrounding normal periodontal the inflammatory reactions . During the pathogenesis
tissue when they are hyperactivated [33,34] . Macrophages of periodontitis, TNF-α not only promote osteoclast
can perform chemotaxis in order to phagocytize foreign maturation and bone resorption, but also reduce the
substances, produce enzymes and many inflammatory activity of periodontal ligament fibroblasts, thus inhibiting
factors, such as prostaglandin E2 (PGE2), IL-1β, and TNF- the differentiation of periodontal ligament fibroblasts
α. These factors play an pivotal role in stimulating the bone into osteoblasts and subsequently resulting in osteoclastic
resorption activities . absorption . PGE2 also is an inflammatory factor that
[46]
[35]
is closely related to the loss of periodontal attachment .
[47]
When bacteria and their products invade periodontal PGE2 has a variety of functions, such as increasing vascular
tissues as antigens, they will induce a kind of specific permeability and chemotactic leukocyte, promoting bone
immune response. Initially, macrophages in dental pulp resorption, and leading to pain occurrence . Similarly,
[48]
matrix and dendritic Langerhans cells within epithelium IL-1β also induces osteoclasts activation, mediates the
and odontoblast layer can take up microbial antigenic synthesis of cyclooxygenase, increases the concentration of
materials and bring them into the lymphoid tissue to activate PGE2 in osteoclasts, and aggravates bone resorption [49,50] . In
lymphocytes . Once lymphocytes reach the damage sites, addition, IL-1β can also enhance the expression of matrix
[36]
B cells will transform to antibody-producing plasma cells, metalloproteinases (MMPs) and increase the degradation
which can produce corresponding antibodies to fight of periodontal extracellular matrix, therefore resulting in
against bacteria . The amount and activity of antibodies the destruction of periodontal tissue . As a polypeptide
[37]
[51]
are considered important factors governing the protection member of the transforming growth factor-β (TGF-β)
effects against chronic periodontitis . When the antigens superfamily of cytokines, TGF-β1 can mediate chemotaxis
[38]
enter periodontal tissue again, they can combine with IgG of neutrophils and fibroblasts as well as promote the
and IgM attached to mast cells; this process can neutralize initiation, growth and differentiation of inflammatory
toxins and assist with the phagocytosis of antigens . cells, which has a high correlation with the occurrence of
[39]
Similarly, if the multivalent antigens binds to the prebound periodontitis .
[52]
IgE, mast cells degranulate and release inflammatory
factors, such as histamine, chemotactic factor, PGE2 and In addition to those mentioned above, there are
[40]
leukotriene, and trigger type I hypersensitivity . also many other inflammatory factors work for the
development of periodontitis. It is worth to note that
In this case, T cells can be activated by antigen-presenting these different inflammatory factors are encapsulated by
cells, while it can also be activated by inflammatory factors different extracellular vesicles to secrete and play various
released by mast cells during the degranulation . T cells physiological roles.
[41]
might contribute to the cell-mediated immune responses
by stimulating various T helper (Th) cell responses: Th1, 3. Formation and physiological functions of
Th2, and Th17, but their specific mechanism and timing of exosomes
their role are still unclear . Although all these cells have
[42]
different roles to play in fighting pathogens, it is worth 3.1. Biogenesis of exosomes
noting that normal immune response can kill bacteria, Extracellular vesicles mainly include ectosomes and
excessive immune response will aggravate inflammatory exosomes, but they are produced via different mechanisms.
reaction and lead to tissue damages . Ectosomes are generated by cells and released through
[43]
plasma membrane budding followed by pinching off, and
2.3. Inflammatory factors are the mediators then released into the extracellular space . However,
[53]
between pathogens and periodontitis
exosomes are generated de novo by cells through the
As a bridge between immune cells and pathogens, endocytosis process and plasma membrane invagination.
inflammatory factors also play an irreplaceable role The invagination of plasma membrane is a cup-shaped
in the occurrence of periodontitis. With the onset of structure that includes cell-surface proteins and soluble
inflammation, the necrotic or apoptotic cells can release proteins, lipids, and nucleic acids, which is driven by
numerous inflammatory mediators, causing vasodilation, endosomal sorting complex required for transport . This
[54]
increasing permeability, and promoting neutrophils, leads to the formation of an early-sorting endosome (ESE),

Volume 1 Issue 2 (2022) 3 https://doi.org/10.36922/gpd.v1i2.99