4.2.2 JAK inhibitors in the in vivo experimental ARDS mouse
model
Suppressing STAT3 activity also have protective effect in LPS-induced
acute lung injury(Zhaoet al., 2016) In a novel sterile injury model of
SPC-TK/SPC-KO (surfactant protein C-thymidine kinase/surfactant protein
C knockout) mice, AZD1480, a JAK1/2 inhibitor decreased hyperactivation
of pSTAT3 and inflammation, reveals the surfactant protein C regulating
JAK/STAT activation in lung repair of ALI(Jin et al., 2018).
In the cecal ligation puncture (CLP) procedure rat model of ALI, the
methotrexate ameliorates systemic inflammation(Bringué et al., 2021).
Natural immunosuppressant compounds, derived from plant sources such as
release of pro-inflammatory cytokines and chemokines. This inhibitory
effect is mediated by altering signal pathways like NF-κB,
JAK/STAT(Peter, Sandeep, Rao & Kalpana, 2020),. Natural astaxanthin
alleviated the risk of cytokine storm (IL-1β, IL-6, IL-8, TNF-α) in
COVID-19 via JAK/STAT signaling(Talukdar, Bhadra, Dattaroy, Nagle &
Dasgupta, 2020).
In the mouse model of ALI, the Src, JAK2, STAT3 are activated. The
tyrosine inhibitor (PP2, SU6656, Tyrphostin A1) significant attenuated
LPS induced ALI determined by histologic and capillary permeability
assays, blocked LPS-dependent cytokine and chemokine production in the
lung and serum(Severgnini et al., 2005b). Oxidative stress imbalance and
apoptosis are the main characters of ventilator-induced lung injury
(VILI), intermedin has anti-oxidative stress and anti-apoptotic effects
via JAK2/STAT3 signaling, thus may prevent and treat the VILI(Fan, He,
Yang & Wang, 2021).