Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 141, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.111835
Keywords
Chloroquine; Mast cells; Thymic stromal lymphopoietin; Caspase-1; Ear edema
Funding
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [2020R1A5A2019413]
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Chloroquine (CQ) exhibits anti-inflammatory effects by modulating TSLP levels in mast cells and reducing ear edema thickness, as well as TSLP levels in ear tissue and serum. The down-regulation of CASP1, NF-kappa B, and other signaling cascades by CQ contributes to its protective role against TSLP-mediated inflammatory disorders.
Thymic stromal lymphopoietin (TSLP) produced by mast cells is involved in allergic inflammation pathogenesis. Chloroquine (CQ) is known to be an anti-malarial drug; however, additional protective functions of CQ have been discovered. This study aims to clarify an anti-inflammatory effect of CQ through modulating TSLP levels using an in vitro model of phorbol myristate acetate (PMA) + A23187-activated human mast cell line (HMC-1) and an in vivo model of PMA-irritated ear edema. CQ treatment reduced the production and mRNA expression levels of TSLP in activated HMC-1 cells. CQ down-regulated caspase-1 (CASP1), MAPKs, and NF-kappa B levels enhanced by stimulation with PMA + A23187. Moreover, ear thickness in ear edema was suppressed following CQ treatment. CQ decreased CASP1 and NF-kappa B levels in the ear tissue. TSLP levels in the ear tissue and serum were reduced following CQ treatment. Collectively, the above findings elucidate that CQ inhibits the proinflammatory mechanisms of TSLP via the down-regulation of distinct intracellular signaling cascade in mast cells. Therefore, CQ may have protective roles against TSLP-mediated inflammatory disorders.
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