Primary Ciliogenesis by 2-Isopropylmalic Acid Prevents PM2.5-Induced Inflammatory Response and MMP-1 Activation in Human Dermal Fibroblasts and a 3-D-Skin Model

Abstract

Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.

2,4,6-Triphenyl-1-hexene, an Anti-Melanogenic Compound from Marine-Derived Bacillus sp. APmarine135

“…However, epidermal hyperdifferentiation was also observed through histological observation (Figure 5D). This is a unique feature of MelanoDerm that we have observed in previous studies [10,[23][24][25]. However, it is also necessary to comprehensively examine whether this phenomenon affected the epidermal pigmentation.…”

L‐Theanine alleviates heat stress through modulation of gut microbiota and immunity

“…Turicibacter can alleviate inflammation, 43 Bifidobacterium can promote intestinal sIgA secretion, 44 and norank_f_Muribaculaceae negatively correlate with inflammatory cytokine levels 48 . Gentisic acid and 2‐isopropylmalic acid also have antioxidant and antibacterial properties 49,50 . In this experiment, LTA maintained immune balance by modulating potentially beneficial microbial communities and amino acid and lipid metabolites.…”

“…48 Gentisic acid and 2-isopropylmalic acid also have antioxidant and antibacterial properties. 49,50 In this experiment, LTA maintained immune balance by modulating potentially beneficial microbial communities and amino acid and lipid metabolites. Specifically, LTA intervention reduced the number of macrophages and downregulated the expression of TAP1, MHC I, and MHC II, thereby decreasing the number of CD4+ T cells and CD8+ T cells, reducing the levels of IFN-γ, TGF-⊎1, IL-17, iNOS, IL-6, and TNF-⊍, and increasing the levels of IL-2, IL-4, and IL-10.…”

Changes in Metabolomic Profiles Induced by Switching from an Erythropoiesis-Stimulating Agent to a Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor in Hemodialysis Patients: A Pilot Study

“…An aliquot (50 µL) of plasma was mixed with 250 µL of a solution containing 55% methanol and 22% chloroform dissolved in distilled water containing 0.045 mg/mL 2-isopropylmalate (the internal standard). Notably, 2-Isopropylmalate is an intermediate formed during leucine biosynthesis, and it can be employed as an internal standard in GC-MS-based human serum metabolomics [ 46 ]. The resulting mixtures were incubated in a Thermomixer C (Eppendorf, Hamburg, Germany) for 30 min at 37 °C with shaking (1200 rpm).…”