Topical application of anthranilate derivatives ameliorates psoriatic inflammation in a mouse model by inhibiting keratinocyte‐derived chemokine expression and neutrophil infiltration

Lin, Zih-Chan; Hsieh, Pei‐Wen; Hwang, Tsong‐Long; Chen, Chi‐Yuan; Sung, Ching-Hwa; Fang, Jia‐You

doi:10.1096/fj.201800354

Cited by 30 publications

(24 citation statements)

References 50 publications

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“…In the imiquimod-induced mouse psoriasis model, topical application of HFP034 could ameliorate the skin lesions and epidermal thickness via inhibition of inflammatory cytokines and chemokines and infiltration of neutrophils. Further investigations suggested that HFP034 increased the skin concentration of cAMP and inhibited the NF-κB activity (Lin et al, 2018 ). These results indicate that topical application of HFP034 tends to be a potential therapeutic option for psoriasis patients.…”

Section: Pde4 Inhibitors Under Development For the Treatment Of Inflamentioning

confidence: 99%

Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases

2018

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Phosphodiesterase-4 (PDE4), mainly present in immune cells, epithelial cells, and brain cells, manifests as an intracellular non-receptor enzyme that modulates inflammation and epithelial integrity. Inhibition of PDE4 is predicted to have diverse effects via the elevation of the level of cyclic adenosine monophosphate (cAMP) and the subsequent regulation of a wide array of genes and proteins. It has been identified that PDE4 is a promising therapeutic target for the treatment of diverse pulmonary, dermatological, and severe neurological diseases. Over the past decades, numerous PDE4 inhibitors have been designed and synthesized, among which roflumilast, apremilast, and crisaborole were approved for the treatment of inflammatory airway diseases, psoriatic arthritis, and atopic dermatitis, respectively. It is regrettable that the dramatic efficacies of a drug are often accompanied by adverse effects, such as nausea, emesis, and gastrointestinal reactions. However, substantial advances have been made to mitigate the adverse effects and obtain better benefit-to-risk ratio. This review highlights the dialectical role of PDE4 in drug discovery and the disquisitive details of certain PDE4 inhibitors to provide an overview of the topics that still need to be addressed in the future.

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Section: Pde4 Inhibitors Under Development For the Treatment Of Inflamentioning

confidence: 99%

Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases

2018

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“…The skin samples were fixed in 10% formalin buffered in phosphate saline for immunohistochemical staining. The detailed procedure was described in the previous study 49 . The skin sections were incubated with anti-IL-6 antibody, anti-IL-17A antibody, anti-Ki67 antibody, and anti-Ly6G antibody for 1 h, and subsequently incubated with biotinylated donkey anti-goat IgG for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Fractional Laser-Mediated siRNA Delivery for Mitigating Psoriasis-like Lesions via IL-6 Silencing

Lee

Lin

Alalaiwe

et al. 2020

Molecular Therapy - Nucleic Acids

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The poor permeability of topically applied macromolecules such as small interfering RNA (siRNA) has inhibited the translation to clinical application. In this study, the fractional CO2 laser-assisted approach was developed to describe siRNA permeation enhancement mediated by the created microchannels for silencing the gene to treat psoriasiform lesions. In vitro permeation using Franz cell and in vivo interleukin (IL)-6 silencing using psoriasis-like plaque in mice were evaluated to verify the impact of the laser irradiation. Low-fluence laser exposure enabled a significant increase in skin transport of siRNA, peptide, and 5-fluorouracil (5-FU). The laser treatment resulted in the enhancement of siRNA flux by 33- and 14-fold as compared to the control in nude mouse and pig skin, respectively. The laser exposure also promoted siRNA penetration across psoriatic and photoaging skins with the deficient barrier, although the enhancement level was minor compared to that of intact skin. The 3D images of confocal microscopy revealed a diffusion of macromolecules into the laser-created microchannels; the radial and vertical distribution to the surrounding and deep tissues followed this. A single laser treatment and the following topical siRNA administration were able to reduce IL-6 expression by 64% in the psoriatic skin model. Laser assistance led to the marked improvement in the plaque and the reduction of specific cytokine expression, keratinocyte proliferation, and neutrophil infiltration. Our data support the use of the fractional laser for delivery of functional nucleic acid into the skin and the target cells.

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“…The levels of interleukin (IL)-6, chemokine (C-C motif) ligand (CCL)5, and CCL17 were measured using commercial kits (ELISA MAX Deluxe Set, BioLegend) based on the manufacturer’s instructions. The detailed procedures for the ELISA assay were described in our previous study (Lin et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

Coenzyme Q0 From Antrodia cinnamomea Exhibits Drug-Resistant Bacteria Eradication and Keratinocyte Inflammation Mitigation to Ameliorate Infected Atopic Dermatitis in Mouse

et al. 2019

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Atopic dermatitis (AD) is an inflammatory skin disease that is usually accompanied by Staphylococcus aureus infection due to cutaneous barrier-function damage. Benzenoid compounds from Antrodia cinnamomea are known to exhibit antibacterial and anti-inflammatory activities. This study sought to investigate the potential of benzenoids for treating bacteria-infected AD. The compounds were screened against methicillin-resistant S. aureus (MRSA). Coenzyme Q0 (CoQ0), a key ingredient in A. cinnamomea, showed the strongest MRSA growth inhibition. We further tested the inhibitory effect of CoQ0 on planktonic and biofilm MRSA. The work was also performed to explore the potential effectiveness of CoQ0 on AD using activated keratinocytes and in vivo experimental AD mice as the models. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CoQ0 against MRSA were 7.81 μg/ml. CoQ0 was found to eradicate biofilm MRSA efficiently and reduce the biofilm thickness. CoQ0 killed MRSA by inhibiting DNA polymerase and topoisomerases. A proteomic assay showed that CoQ0 also reduced the ribosomal proteins. In the anti-inflammation study, CoQ0 was found to downregulate the expression of interleukin (IL)-6, chemokine (C-C motif) ligand (CCL)5, and CCL17 in HaCaT cells. CoQ0 at 0.5 μg/ml could recover the filaggrin decreased by HaCaT activation to the normal control. We established a bacteria-infected AD-like model in mice using ovalbumin (OVA) and topically applied MRSA. Topical CoQ0 delivery lessened the MRSA presence in the AD-like lesions by >90%. The erythema, barrier function, and epidermal thickness of the AD-like wounds were improved by CoQ0 through the reduction of IL-1β, IL-4, IL-6, IL-10, interferon (IFN)-γ, and by neutrophil infiltration in the lesional skin. CoQ0 is therefore regarded as effective in mitigating AD symptoms associated with bacterial load.

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Topical application of anthranilate derivatives ameliorates psoriatic inflammation in a mouse model by inhibiting keratinocyte‐derived chemokine expression and neutrophil infiltration

Cited by 30 publications

References 50 publications

Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases

Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases

Fractional Laser-Mediated siRNA Delivery for Mitigating Psoriasis-like Lesions via IL-6 Silencing

Coenzyme Q0 From Antrodia cinnamomea Exhibits Drug-Resistant Bacteria Eradication and Keratinocyte Inflammation Mitigation to Ameliorate Infected Atopic Dermatitis in Mouse

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