Triptolide inhibits transforming growth factor‐β₁‐induced proliferation and migration of rat airway smooth muscle cells by suppressing nuclear factor‐κB but not extracellular signal‐regulated kinase 1/2

Abstract

SummaryAirway remodelling contributes to increased mortality in asthma. We have reported that triptolide can inhibit airway remodelling in a mouse asthma model. In this study, we aimed to investigate the effect of triptolide on proliferation and migration of airway smooth muscle cells (ASMC), and the possible mechanism. Rat ASMC were cultured and synchronized, then pre-treated with different concentrations of triptolide before being stimulated by transforming growth factor-b 1 (TGF-b 1 ). Cell proliferation was evaluated by cell counting and MTT assay. Flow cytometry was used to study the influence of triptolide on the cell cycle. Migration was measured by Transwell analysis. Signal proteins [nuclear factor-jB (NF-jB) p65 and extracellular signal-regulated kinase 1/2 (ERK1/2)] were detected by Western blotting. A lactate dehydrogenase releasing test and flow cytometry analysis of apoptosis were also performed to explore the potential cytotoxic or pro-apoptotic effects of triptolide. Triptolide significantly inhibited TGF-b 1 -induced ASMC proliferation and migration (P < 0Á05). The cell cycle was dose-dependently blocked at G1/S-interphase by triptolide. Western blotting analysis showed that TGF-b 1 -induced NF-jB p65 phosphorylation was inhibited by triptolide pre-treatment, but ERK1/2 was not affected. No cytotoxic or pro-apoptotic effects were detected under the concentration of triptolide that was used. Triptolide may function as an inhibitor of asthma airway remodelling by suppressing ASMC proliferation and migration through inactivation of the NF-jB pathway.

Therapeutic Potential of Triptolide as an Anti-Inflammatory Agent in Dextran Sulfate Sodium-Induced Murine Experimental Colitis

“…Triptolide, the main biologically active substance in Tripterygium wilfordii Hook F. (TwHF), was previously demonstrated to possess powerful anti-inflammatory and immunosuppressive properties in many preclinical studies (38,39). Triptolide was found to regulate multiple inflammatory mediators in vitro and in animal models of inflammation and autoimmune diseases such as nephritis, asthma, and arthritis (40)(41)(42). Some studies also found that triptolide can relieve the intestinal inflammation of the chronic colitis observed in IL-10 −/− mice (43,44).…”

Wnt/β‑catenin signaling pathway regulates asthma airway remodeling by influencing the expression of c‑Myc and cyclin D1 via the p38 MAPK‑dependent pathway

“…Samples were then cultured in DMEM (Thermo Fisher Scientific, Inc.) containing 20% fetal bovine serum (Thermo Fisher Scientific, Inc.) in a humidified atmosphere with 5% CO 2 at 37°C. ASMCs were identified by observing the typical ‘hill and valley’ growth pattern (18) and via the immunocytochemistry staining of α-smooth muscle actin (1:100; Abcam; cat. no.…”

Eupatilin alleviates airway remodeling via regulating phenotype plasticity of airway smooth muscle cells

“…Fang et al [12] addressed that TGF-β1 induces ASMCs proliferation and migration. Chen et al [13] demonstrated that triptolide functions as an inhibitor of asthma airway remodeling, which is evidenced by the inhibition of TGF-β1 induced ASMCs proliferation and migration. In the present study, we found that eupatilin suppressed cell proliferation and migration in TGF-β1-induced ASMCs, suggesting that eupatilin might have the ability to change the phenotype plasticity.…”