Tanreqing Injection Regulates Cell Function of Hypoxia-Induced Human Pulmonary Artery Smooth Muscle Cells (HPASMCs) through TRPC1/CX3CL1 Signaling Pathway

Abstract

Hypoxia-induced pulmonary arterial hypertension (HPAH) is due to hypoxia caused by vascular endothelial cell remolding and damage. Previous studies have suggested that CX3CL1 plays an important role in HPAH which is affected by oxidative stress. Ca2+ channel activation correlated with increasing NF-κB levels induced by ROS. Tanreqing injection (TRQ) is a traditional Chinese medicine (TCM) for acute upper respiratory tract infection and acute pneumonia. In the present study, we explored the effect of TRQ on human pulmonary artery smooth muscle cells (HPASMCs) undergoing hypoxia and feasible molecular mechanisms involved in. Cell proliferation was assayed using CCK8 kits. Immunofluorescence and western blotting along with ELISA assay were performed to investigate the effect of TRQ on hypoxia-induced ROS, Ca2+, hydroxyl free radicals, and the expression of Ca2+ channel protein TRPC1, CX3CR1, HIF-1α, NF-κBp65, and p-NF-κBp65 in HPASMCs. Human CX3CL1 and the inhibitor of TRPC1 as SKF96365 were used for further investigation. TRQ inhibited hypoxia-induced increasing cell adhesion, ROS, Ca2+, hydroxyl free radicals, CX3CR1, HIF-1α, NF-κBp65 activation, and even on TRPC1 expression in HPASMC which tended to be attenuated even reversed by CX3CL1. Our results suggested that TRQ might help to attenuate remodeling of HPASMC through inhibiting the ROS and TRPC1/CX3CL1 signaling pathway.

The role of immune cells and inflammation in pulmonary hypertension: mechanisms and implications

“…Under the pathological condition of PH, CX3CL1 led to the adhesion of macrophages expressing CX3CR1 to PAECs, which led to PAECs dysfunction and trigger perivascular inflammatory reaction ( 75 ). In addition, CX3CL1 promoted the proliferation of pericytes and PASMCs, which further aggravated the remodeling of pulmonary small vessels, leading to further aggravation of PH ( 76 ). CX3CR1 deficiency protected against HPH by modulating monocyte recruitment, macrophage polarization, and PAMCs proliferation ( 35 ).…”

Inflammation and immunity in the pathogenesis of hypoxic pulmonary hypertension

“…CX3CL1/Fractalkine expression was significantly upregulated in pulmonary microvascular endothelial cells from high-altitude individuals, patients with obstructive lung disease, and mice (33). CX3CL1 promotes the proliferation of pericytes and smooth muscle cells, which in turn aggravates pulmonary small-vessel myelination, causing pulmonary hemodynamic changes and RV hypertrophy (154). In addition, CX3CL1 can worsen HPH by regulating monocyte recruitment and macrophage polarization (25).…”

Tanreqing injection inhibits dengue virus encephalitis by suppressing the activation of NLRP3 inflammasome

“…Tanreqing injection (TRQ), consisting of Scutellaria baicalensis Georgi (Lamiaceae), Selenaretos thibetanus Cuvier (Ursidae), Capra hircus Linnaeus (Bovidae), Forsythia suspensa (Thunb.) Vahl (Oleaceae) and Lonicera japonica Thunb (Caprifoliaceae), is a new type of Chinese medicine (TCM) with antipyretic, antiviral, antibacterial, and anti-convulsion effects [ 12 ]. The multicomponent mixture in TRQ was screened and identified by HPLC–DAD-TOF/MS and 12 compounds were confirmed by online ESI-TOF/MS [ 13 , 14 ].…”

“…Moreover, these compounds have been demonstrated to exert anti-inflammatory effects to treat various inflammation-related diseases [ 24 – 27 ]. Clinically, TRQ is mainly used for the treatment of infantile acute pneumonia, acute upper respiratory tract infection, acute cerebral ischemia and acute cholecystitis [ 12 , 28 ]. TRQ has been used in the treatment of brain-related diseases.…”