Isoforskolin and forskolin attenuate lipopolysaccharide‐induced inflammation through TLR4/MyD88/NF‐κB cascades in human mononuclear leukocytes

Abstract

The principal active component of isoforskolin (ISOF) is from the plant Coleus forskohlii , native to China, which has attracted much attention for its biological effects. We hypothesize that ISOF and forskolin (FSK) pretreatment attenuates inflammation induced by lipopolysaccharide (LPS) related to toll‐like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B (NF‐κB) signaling. Mononuclear leukocytes (MLs) from healthy donors' blood samples were separated by using density gradient centrifugation. Protein levels of TLR4, MyD88, and NF‐κB were detected using western blot and inflammatory cytokines interleukin (IL) 1β, IL‐2, IL‐6, IL‐21, IL‐23, tumor necrosis factor (TNF) α, and TNF‐β were tested by enzyme‐linked immunosorbent assay and Quantibody array in MLs. Our results showed that LPS augmented the protein levels of TLR4, MyD88, and NF‐κB in MLs and the production of IL‐1β, IL‐2, IL‐6, IL‐21, IL‐23, TNF‐α, and TNF‐β in supernatants of MLs. Despite treatment with ISOF and FSK prior to LPS, the protein levels of TLR4, MyD88, NF‐κB, IL‐1β, IL‐2, IL‐6, IL‐21, IL‐23, TNF‐α, and TNF‐β in MLs were apparently decreased. roflumilast (RF) and dexamethasone (DM) had a similar effect on MLs with ISOF and FSK. Our results, for the first time, have shown that ISOF and FSK attenuate inflammation in MLs induced by LPS through down‐regulating protein levels of IL‐1β and TNF‐α, in which TLR4/MyD88/NF‐κB signal pathway could be involved.

The Role of Serotonin in Concanavalin A-Induced Liver Injury in Mice

“…Kappa B (NF-κB) in Con A-Treated Mice. NF-κB is one of the families of transcriptional factor proteins, which participates in inflammatory responses, oxidative stress, and apoptosis and regulates a variety of inflammatory factors such as IL-2, IL-6, and TNF-α [28][29][30]. The protein expression of NF-κB was further detected in ALI mice, and the result showed that intrahepatic p-p65 was markedly elevated after Con A injection.…”

“…Pathway in Con A-Treated Mice. As one of the earliest discovered pattern recognition receptors, TLRs are involved in inflammatory response and NF-κB activation [28,31]. Moreover, Con A stimulates the expression of TLR2, TLR4, and TLR9 and downstream pathways in liver tissue, resulting in the release of numerous proinflammatory factors [12,13].…”

New Insights into Pathomechanisms and Treatment Possibilities for Lung Silicosis

“…cAMP then binds to the NLRP3 protein and targets it for degradation, thus interrupting the action of inflammasome and production of IL-1β in human macrophages [162]. However, forskolin may also down-regulate the protein levels of IL-1β and TNFα by influencing the TLR4/MyD88/NF-κB signal pathway [163].…”

Characterization of Burn Eschar Pericytes

“…In addition, they showed that pericyte stimulation with TGF-β1 and IL-1β has a synergistic release of IL-6 [40] which correlates with our finding that IL-1βis upregulated (Table 2) and a 5 fold increase in IL-6 expression ( Figure 3a). MyD88, an upstream regulator of interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) expression [41,42] was also examined. We found expression of MyD88 was increased in the burn eschar derived-pericytes compared to normal skin derived-pericytes ( Figure 4b).…”