2.5 ARDS
ARDS was known as non-cardiogenic respiratory failure
with severely impaired pulmonary function, hypoxemia, and decreased
pulmonary compliance, with around 30 million patients every
year[101] and mortality rate ranging from 34.9% to 46.1% depending
on the severity[102]. ARDS is caused by pulmonary infections
(bacterial, viral, etc.), other significant infections (skin,
genitourinary system, etc.), burns, particularly smoke inhalation, and
all kinds of traumas[103]. There are no specialized treatment
options, and therapy is still reliant on lung-protective mechanical
ventilation.
When microorganisms, irritant mediators, and so on infiltrate the
alveolar barrier, macrophages polarize from resident alveolar
macrophages to the M1 phenotype at an early stage in response to
Toll-like receptors (TLR) induced by infection, releasing
pro-inflammatory factors such as IL-1, IL-6, and TNF-α, which are the
first hurdle of lung immune response[104], while pro-inflammatory
Inflammation is exacerbated by further activation and release of
pro-inflammatory factors, chemokines, adhesion molecules, and so on. The
main mechanism of ARDS is assumed to be the acute, widespread lung
inflammation caused by this overwhelming immune response [105].
A large number of miRNAs, such as miR-146, miR-155, miR-221, and
miR-222, have been noted to be stimulated upon TLR signaling activation,
and lncRNAs such as Mirt2, THRIL, MALAT1, and lincRNA-21 are also
altered upon TLR activation and negatively regulate TLR signaling as
well as suppress pro-inflammatory factor expression[106]. MALAT1 is
highly expressed in inflammation-activated macrophages, interacts with
NF-κB, inhibits TLR signaling, and lowers TNF-α, IL-6 and other
inflammatory factors [107]. HOTAIR affects the miR-30a-5p/PDE7A axis
in LPS-induced ARDS, increases the release of inflammatory factors, and
exacerbates the pulmonary inflammatory response[108].