Common Chronic Inflammatory Disease Research Articles

Effectiveness of low-level laser therapy in reducing pain score and healing time of recurrent aphthous stomatitis: a systematic review and meta-analysis

BackgroundRecurrent aphthous stomatitis (RAS) is a common chronic inflammatory oral disease that negatively impacts the quality of life. Current therapies aim to reduce pain and healing process yet challenges such as rapid loss due to salivary flushing in topical drugs and adverse effects due to prolonged use of systemic medications require further notice. Low-level laser therapy is reported with immediate pain relief and faster healing thus preserving the potential for optimal treatment modalities. This review critically analyses and summarizes the effectiveness of LLLT in reducing pain scores and healing time of RAS.MethodsA systematic search was conducted in ScienceDirect, PubMed, and Scopus using keywords of low-level laser therapy, photo-biomodulation therapy, and recurrent aphthous stomatitis. RCTs between 1967 to June 2022, presenting characteristics of the laser and reporting pain score and/or healing time of RAS after irradiation were included. Animal studies and recurrent aphthous ulcers with a history of systemic conditions were excluded. Studies were critically appraised using the RoB 2 tool. A meta-analysis was performed using inverse variance random effects.ResultsFourteen trials with a total of 664 patients were included. Reduced pain was reported in 13 studies, while shortened healing time was presented in 4. The pooling of two studies after CO2 irradiation demonstrated faster healing time compared to placebo (MD − 3.72; 95% CI − 4.18, − 3.25).ConclusionPain score and healing time of RAS were reduced after irradiation with LLLT. RoB resulted in “some concerns” urging well-designed RCTs with larger samples to further assess each laser application for comparison.Systematic review registrationPROSPERO CRD42022355737.

Atopic Dermatitis and Psoriasis: Similarities and Differences in Metabolism and Microbiome.

Atopic dermatitis and psoriasis are common chronic inflammatory diseases of high incidence that share some clinical features, including symptoms of pruritus and pain, scaly lesions, and histologically, acanthosis and hyperkeratosis. Meanwhile, they are both commonly comorbid with metabolic disorders such as obesity and diabetes, indicating that both diseases may exist with significant metabolic disturbances. Metabolomics reveals that both atopic dermatitis and psoriasis have abnormalities in a variety of metabolites, including lipids, amino acids, and glucose. Meanwhile, recent studies have highlighted the importance of the microbiome and its metabolites in the pathogenesis of atopic dermatitis and psoriasis. Metabolic alterations and microbiome dysbiosis can also affect the immune, inflammatory, and epidermal barrier, thereby influencing the development of atopic dermatitis and psoriasis. Focusing on the metabolic and microbiome levels, this review is devoted to elaborating the similarities and differences between atopic dermatitis and psoriasis, thus providing insights into the intricate relationship between both conditions.

Role of IL‐5 in asthma and airway remodelling

AbstractAsthma is a common and burdensome chronic inflammatory airway disease that affects both children and adults. One of the main concerns with asthma is the manifestation of irreversible tissue remodelling of the airways due to the chronic inflammatory environment that eventually disrupts the whole structure of the airways. Most people with troublesome asthma are treated with inhaled corticosteroids. However, the development of steroid resistance is a commonly encountered issue, necessitating other treatment options for these patients. Biological therapies are a promising therapeutic approach for people with steroid‐resistant asthma. Interleukin 5 is recently gaining a lot of attention as a biological target relevant to the tissue remodelling process. Since IL‐5‐neutralizing monoclonal antibodies (mepolizumab, reslizumab and benralizumab) are currently available for clinical use, this review aims to revisit the role of IL‐5 in asthma pathogenesis at large and airway remodelling in particular, in addition to exploring its role as a target for biological treatments.

Tanshinol ameliorates imiquimod-induced psoriasis by inhibiting M1 macrophage polarization through suppression of the notch signaling pathway.

Psoriasis is a common immune-related chronic inflammatory skin disease, often accompanied by significant itching, and once diseased, the course of the disease lasts for most of the lifetime. Tanshinol (TAN) is an active ingredient of Salvia miltiorrhiza, which possesses pharmacological effects such as anti-inflammatory and antioxidant properties. However, the effects of TAN on psoriasis have not been widely reported. Therefore, the aim of this study was to investigate the therapeutic effects and mechanisms of TAN in psoriasis. An imiquimod (IMQ)-induced psoriasis mouse model was constructed and treated with different doses of TAN to observe the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. Further removal of macrophages or inhibition or activation of Notch signaling pathway was performed to examine the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. In addition, in vitro experiments verified that TAN regulates RAW264.7 macrophage polarization and cytokine secretion through the Notch pathway. The results showed that TAN alleviated IMQ-induced skin lesions and pathological phenotypes in psoriasis mice and inhibited Notch signaling pathway and M1-type macrophage polarization. Moreover, macrophage clearance and Notch signaling pathway activation inhibited the effect of TAN on psoriasis. Further in vitro experiments showed that Notch agonists reversed the effects of TAN on macrophage polarization and inflammatory cytokines. Collectively, these findings suggest that TAN may exert a therapeutic effect on psoriasis by inhibiting the Notch signaling pathway and thus M1-type macrophage polarization.

Anti-Müllerian hormone (ovarian reserve) in rheumatoid arthritis patients: correlation with disease activity

BackgroundRheumatoid arthritis is considered one of the most common chronic inflammatory autoimmune diseases that lead to affection of several joints, as well as extra-articular organ involvement.Rheumatoid arthritis women tend to menopause somewhat earlier. This was attributed to primary ovarian insufficiency because of autoimmune disorders. Anti-Müllerian hormone is a marker used for evaluating preantral follicle reserve. It provides a very sensitive way to reflect the ovarian reserve and has become a crucial factor in determining it.The study aimed to show the influence of rheumatoid arthritis and its activity on ovarian reserve assessed using anti-Müllerian hormone serum levels.ResultsOur cross-sectional study involved 30 rheumatoid arthritis female patients with an age range between 25 and 35 years. The Disease Activity Score (DAS 28-ESR) was used to assess the degree of disease activity. Serum level of anti-Müllerian hormone was determined using quantitative enzyme-linked immunosorbent assay and the correlation with the disease activity as well as with the medications the patients were receiving was analyzed. A statistically significant relation was found amid the disease activity and the anti-Müllerian hormone level. Serum levels of anti-Müllerian hormone were found less in cases with high disease activity than in low to moderate cases. Different medications had no effect on anti-Müllerian hormone levels.ConclusionsRheumatoid arthritis high disease activity was linked to a diminished level of serum anti-Müllerian hormone.

GPR15LG regulates psoriasis-like inflammation by down-regulating inflammatory factors on keratinocytes.

Psoriasis is a common chronic inflammatory skin disease characterized by aberrant proliferation of keratinocytes and infiltration of immune cells. We previously found that GPR15LG protein is highly expressed in psoriasis lesional skin and it positively regulates psoriatic keratinocyte proliferation. Our data also showed that GPR15LG could regulate the activity of NF-κB pathway, which is associated with psoriatic inflammation. In the present study, we demonstrated that Gpr15lg (ortholog of GPR15LG) knockdown attenuated the severity of imiquimod (IMQ)-induced psoriasis-like inflammation in mice. Such an effect was achieved by down-regulating the expression of inflammatory cytokines interleukin (IL)-1α, IL-1β, tumor necrosis factor (TNF)-α and S100A7. Consistently, GPR15LG knockdown in vitro significantly downgraded the expression of inflammatory factors in the cellular model of psoriasis. These results suggested that GPR15LG could be involved in the development of psoriasis by regulating inflammation.

Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production.

Psoriasis is a common chronic inflammatory skin disease driven by the aberrant activation of dendritic cells (DCs) and T cells, ultimately leading to increased production of cytokines such as interleukin (IL)-23 and IL-17A. It is established that the cGAS-STING pathway is essential for psoriatic inflammation, however, the specific role of cGAS-STING signaling in DCs within this context remains unclear. In this study, we demonstrated the upregulation of cGAS-STING signaling in psoriatic lesions by analyzing samples from both clinical patients and imiquimod (IMQ)-treated mice. Using a conditional Sting-knockout transgenic mouse model, we elucidated the impact of cGAS-STING signaling in DCs on the activation of IL-17- and IFN-γ-producing T cells in psoriatic inflammation. Ablation of the Sting hampers DC activation leads to decreased numbers of IL-17-producing T cells and Th1 cells, and thus subsequently attenuates psoriatic inflammation in the IMQ-induced mouse model. Furthermore, we explored the therapeutic potential of the STING inhibitor C-176, which reduces psoriatic inflammation and enhances the anti-IL-17A therapeutic response. Our results underscore the critical role of cGAS-STING signaling in DCs in driving psoriatic inflammation and highlight a promising psoriasis treatment.

Role of interleukin-17 in juvenile idiopathic arthritis

Joint diseases is a pressing problem of pediatrics. Juvenile idiopathic arthritis is a common chronic systemic inflammatory disease of the joints in children; its etiological factors remain completely unknown. The disease can affect children of any age and is characterized by a long progressive course, leading to the development of contractures and functional failure, and thereby disability. According to the authors of the article, the content of the interleukin-17 in the blood serum of children with juvenile idiopathic arthritis depends on the duration of the disease, as well as its severity.

Construction of janus mesenchymal stem cell-hitchhiked melanin nanoparticles to modulate the Th17/Treg balance for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is a common chronic inflammatory disease capable of causing the disability. Although various antioxidant strategies have been attempted for prevention and treatment of RA through scavenging the free radicals, the therapeutic effect is limited. Recently, it is reported that the unremitting course of RA intensely correlates with the persistence of immunologic memory, in which the imbalance of T helper 17 (Th17) cells/regulatory T (Treg) cells plays an important role. Herein, we constructed Janus mesenchymal stem cell (MSC)-hitchhiked melanin nanoparticles (MSCFM) for RA therapy, where one half of MSC kept intact for chemotactically migrating towards the RA inflammatory sites and efficiently restoring the Th17/Treg balance based on the property of MSCs, while the other half hitchhiked the iron-doped melanin (FM) nanoparticles (NPs) and release them to scavenge free radicals for maintaining the durability of Th17/Treg balance. In vitro studies indicated MSCFM could migrate towards CXCL12 inflammatory cytokine, scavenge reactive oxygen and nitrogen species, inhibit Th17 cell proliferation and induce Treg cell production. Further in vivo studies corroborated that intravenously injected MSCFM could target the RA site of collagen-induced arthritis mouse model and alleviate the pathological progression of RA. MSCFM holds great potential as an anti-inflammatory agent for RA management.

Barriers to care and health-related quality of life among US adults with several common chronic inflammatory skin diseases: a cross-sectional analysis of the NIH All of Us Research Program.

Research investigating the impact of barriers to care on health-related quality of life (HRQoL) among US adults with chronic inflammatory skin diseases (CISDs) is limited. In this study, we utilize multivariable-adjusted logistic regression to analyze the associations between cost barriers (e.g., delaying specialist and mental health care due to cost) and non-cost barriers (e.g., delaying care due to transportation issues and the lack of provider diversity) with HRQoL among US adults with several common CISDs in the National Institutes of Health's All of Us Research Program (AoURP). Among the 19,208 adults with CISDs included in our analysis, the prevalence of poorer HRQoL(i.e., "fair" or "poor" HRQoL) was significantly higher among adults with CISDs who experienced cost (aOR, 2.39;95% CI, 2.10-2.73) and non-cost barriers (aOR, 2.52; 95% CI, 2.20-2.88) than those with CISDs who did not experience those barriers. Since dermatologists are often the only physician caring for patients with CISDs, this study reinforces the critical role dermatologists have in addressing social determinants of health and advocating to reduce cost and non-cost barriers for their patients with CISDs.

Abrocitinib-associated adverse events: a real-world pharmacovigilance study using the FAERS database

ABSTRACT Background Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Janus kinase (JAK) modulates cytokines involved in AD pathophysiology, and JAK inhibitors have emerged as effective pharmacotherapeutic remedies for AD. Abrocitinib, an oral selective inhibitor of JAK1, is indicated for the management of moderate-to-severe AD. The current study evaluated the adverse events (AEs) associated with abrocitinib in a real-world setting. Methods To quantify the signals of abrocitinib-associated AEs, we used the US Food and Drug Administration Adverse Event Reporting System (FAERS) for this pharmacovigilance study with two established pharmacovigilance methods. Results A total of 1071 AEs of abrocitinib were investigated as the primary suspected from the FAERS to detect and characterize relevant safety signals. The analysis revealed 85 signals for abrocitinib. The most common AE for abrocitinib was drug ineffective. The signal strength of eczema herpeticum was 515.87 (277.80–957.98) and 510.59 (5148.65) and exhibited the highest strength for abrocitinib. Rare AEs such as aggravated condition, pruritus, and hypersensitivity were not listed on the label, and attention to these AEs is required. Conclusion The analysis of the AE signals may provide support for clinical monitoring and risk identification of abrocitinib.

The shared circulating diagnostic biomarkers and molecular mechanisms of systemic lupus erythematosus and inflammatory bowel disease.

Systemic lupus erythematosus (SLE) is a multi-organ chronic autoimmune disease. Inflammatory bowel disease (IBD) is a common chronic inflammatory disease of the gastrointestinal tract. Previous studies have shown that SLE and IBD share common pathogenic pathways and genetic susceptibility, but the specific pathogenic mechanisms remain unclear. The datasets of SLE and IBD were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the Limma package. Weighted gene coexpression network analysis (WGCNA) was used to determine co-expression modules related to SLE and IBD. Pathway enrichment was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for co-driver genes. Using the Least AbsoluteShrinkage and Selection Operator (Lasso) regressionand Support Vector Machine-Recursive Feature Elimination (SVM-RFE), common diagnostic markers for both diseases were further evaluated. Then, we utilizedthe CIBERSORT method to assess the abundance of immune cell infiltration. Finally,we used the single-cell analysis to obtain the location of common diagnostic markers. 71 common driver genes were identified in the SLE and IBD cohorts based on the DEGs and module genes. KEGG and GO enrichment results showed that these genes were closely associated with positive regulation of programmed cell death and inflammatory responses. By using LASSO regression and SVM, five hub genes (KLRF1, GZMK, KLRB1, CD40LG, and IL-7R) were ultimately determined as common diagnostic markers for SLE and IBD. ROC curve analysis also showed good diagnostic performance. The outcomes of immune cell infiltration demonstrated that SLE and IBD shared almost identical immune infiltration patterns. Furthermore, the majority of the hub genes were commonly expressed in NK cells by single-cell analysis. This study demonstrates that SLE and IBD share common diagnostic markers and pathogenic pathways. In addition, SLE and IBD show similar immune cellinfiltration microenvironments which provides newperspectives for future treatment.

PA28γ induces dendritic cell maturation and activates T-cell immune responses in oral lichen planus.

Oral lichen planus (OLP) is a common chronic inflammatory disease of the oral mucosa, the mechanism of its inflammatory progression has not yet been fully elucidated. PA28γ plays a significant role in a variety of immune-related diseases. However, the exact role of PA28γ in the pathogenesis of OLP remains unclear. Here, we demonstrated that PA28γ is overexpressed in epithelial cells and inflammatory cells of OLP tissues but has no significant relationship with OLP subtypes. Functionally, keratinocytes with high PA28γ expression could induce dendritic cell (DC) maturation and promote the T-cell differentiation into Th1 cells in response to the immune response. In addition, we found that a high level of PA28γ expression is associated with high numbers of infiltrating mature DCs and activated T-cells in OLP tissues. Mechanistically, keratinocytes with high PA28γ expression could promote the secretion of C-C motif chemokine (CCL)5, blocking CCL5 or/and its receptor CD44 could inhibit the induction of T-cell differentiation by keratinocytes with high PA28γ expression. In conclusion, we reveal that keratinocytes with high expression of PA28γ in OLP can induce DC maturation and promote T-cell differentiation through the CCL5-CD44 pathway, providing previously unidentified mechanistic insights into the mechanism of inflammatory progression in OLP.

Specific delivery of metronidazole using microparticles and thermosensitive in situ hydrogel for intrapocket administration as an alternative in periodontitis treatment

Periodontitis is a common chronic inflammatory disease primarily caused by the prevalence of bacterial overgrowth resulting in the development of an inflammatory condition that destroys the tooth’s supporting tissues and eventual tooth loss. Comparatively, to other treatment methods, it is difficult for topical antibacterial drugs to effectively permeate the biofilm’s physical barrier, making conventional therapy for periodontitis more challenging. This novel study combines thermosensitive in situ hydrogel with microparticles (MPs) to enhance the targeted delivery of metronidazole (MET) to the periodontal pocket. Polycaprolactone (PCL) polymer was utilized to produce bacteria-sensitive MPs. Additionally, the study assessed the attributes of MPs and demonstrated an enhancement in the in vitro antibacterial efficacy of MPs towards Staphylococcus aureus (SA) and Escherichia coli (EC). Subsequently, we incorporated MET-MPs into thermosensitive in situ hydrogel formulations using chitosan. The optimized formulations exhibited stability, appropriate gelation temperature, mucoadhesive strength, and viscosity. In vitro permeation tests showed selective and prolonged drug release against SA and EC. Ex vivo experiments demonstrated no significant differences between in situ hydrogel containing pure MET and MET–MPs in biofilm quantity, bacterial counts, and metabolic activity in biofilms. According to in vitro tests and the effectiveness of the antibacterial activity, this study has exhibited a novel methodology for more efficacious therapies for periodontitis. This study aims to utilize MET in MPs to improve its effectiveness, enhance its antibacterial activity, and improve patient treatment outcomes. In further research, the efficacy of the treatment should be investigated in vivo using an appropriate animal model.

Reflectance confocal microscopy and clinical evaluation of a product containing Silybum marianum fruit extract in monotherapy for acne vulgaris treatment: A prospective study

AbstractBackgroundAcne is a common pilosebaceous unit chronic inflammatory disease, with a multifactorial pathogenesis. It involves several processes: increased sebum production, alteration of the follicular keratinization process and bacterial colonization by Cutibacterium acnes.ObjectivesTo evaluate the effectiveness of reflectance confocal microscopy (RCM) in evaluating the reduction of mild to severe acne lesions in patients treated with an investigational product containing Silybum marianum fruit extract (SMFE).MethodsSubjects previously examined for counting acne lesions were topically treated in the face, with an investigational product containing SMFE in monotherapy over the course of 60 days (n = 31). They were examined for counting acne lesions. Efficacy and quality of life, tolerability, and safety assessments were performed. The infundibular diameter (ID) measurement of normal and acne skin areas was analyzed using RCM.ResultsThe RCM data statistical analysis allowed us to identify two ID patterns, 300–750 µm, with a reduction of 33.33% (p < 0.05) and 900–1050 µm with 73.16% (p < 0.05) reduction after 60 days. The noninflammatory lesions had a mean variation of −44.51% and −67.82% after 30 and 60 days, respectively (t test: p < 0.05 and p < 0.001 after Bonferroni's correction). The inflammatory lesions had a mean variation of −69.31% and −79.40% after 30 and 60 days (t test: p < 0.05 and p = 0.118 after Bonferroni's correction).ConclusionsThe authors demonstrated the effectiveness of the monotherapy scheme with an investigational product containing SMFE through the statistically significant results obtained by the RCM in acneic and nonacneic skin, in addition to the reduction in the number of noninflammatory at the end of the 60 days of clinical follow‐up. Furthermore, the monotherapy scheme with the investigational product proved safe, with no serious adverse events during the entire clinical study. In summary, the use of RCM proved to be effective in assessing the therapeutic response in patients with moderate to severe acne.

Polylysine-derived carbon quantum dots modulate T lymphocyte responses for periodontitis treatment

Periodontitis, a common chronic inflammatory disease, is characterized by T cell responses leading to gradual alveolar bone loss and eventual tooth mobility or loss. Herein, polylysine-derived carbon quantum dots (PLL-CQDs) are synthesized via the pyrolysis method to facilitate the recovery of periodontal bone loss induced by periodontitis by modulating T cell phenotype. The PLL-CQDs, characterized by small particle size (2.31 ± 0.70 nm) and fluorescence properties, preserved the positive charge of PLL, affirming successful preparation. In vitro studies revealed that PLL-CQDs significantly increased T cell proliferation in a concentration-dependent manner, while effectively suppressing differentiation into CD4+ phenotype. Furthermore, they promoted alkaline phosphatase expression and calcium nodule formation in MC3T3-E1 cells, indicating potential for periodontal bone regeneration. In vivo experiments demonstrated that PLL-CQDs mitigated alveolar bone resorption and modulated periodontal tissue inflammation. Overall, PLL-CQDs exhibited the ability to regulate T cell differentiation and expedite periodontal bone healing, offering promising implications for periodontitis treatment and suggesting novel strategies for addressing immune-associated bone diseases using CQDs.

TRPV3 promotes sebocyte inflammation via transcriptional modulating TLR2 in acne

Acne is a common chronic inflammatory disease of the pilosebaceous unit. Transient receptor potential vanilloid 3 (TRPV3) is an ion channel that is involved in inflammatory dermatosis development. However, the involvement of TRPV3 in acne-related inflammation remains unclear. Here, we used acne-like mice and human sebocytes to examine the role of TRPV3 in the development of acne. We found that TRPV3 expression increased in the skin lesions of Propionibacterium acnes (P. acnes)-injected acne-like mice and the facial sebaceous glands (SGs) of acne patients. TRPV3 promoted inflammatory cytokines and chemokines secretion in human sebocytes and led to neutrophil infiltration surrounding the SGs in acne lesions, further exacerbating sebaceous inflammation and participating in acne development. Mechanistically, TRPV3 enhanced TLR2 level by promoting transcriptional factor phosphorylated-FOS-like antigen-1 (p-FOSL1) expression and its binding to the TLR2 promoter, leading to TLR2 upregulation and downstream NF-κB signaling activation. Genetic or pharmacological inhibition of TRPV3 both alleviated acne-like skin inflammation in mice via the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebaceous inflammation and indicated its potential as an acne therapeutic target.

Clinical efficacy of modern emollients in atopic dermatitis: case reports

Atopic dermatitis is the most common chronic inflammatory skin disease, characterized by itching, chronic recurrent course, and in most cases is associated with respiratory allergies ― allergic rhinitis and asthma. The incidence of atopic dermatitis varies from 15 to 30% or more among children and from 2 to 14% among adults in different countries. The pathophysiological mechanisms of atopic dermatitis are based on a genetic predisposition to allergies, immune dysregulation, and the influence of environmental factors. Recent studies have shown that a key feature of atopic dermatitis is a barrier defects in compromised skin which leads to increased permeability and penetration of environmental factors (e.g., microbes, allergens) and finally to allergen sensitization and to the development of specific allergic inflammation in the target organ ― the skin.
 The article presents a series of clinical cases of moderate and severe atopic dermatitis, demonstrated an integrated approach to the treatment and selection of emollients, considering the phenotypic features of atopic dermatitis.

Influence of Clinical and Psychosocial Factors on the Adherence to Topical Treatment in Psoriasis.

(1) Background: Psoriasis is a common chronic inflammatory skin disease with different manifestations, affecting the quality of life at social, emotional, and professional dimensions and requiring long-term treatment. This study aimed to investigate the effect of psychosocial and clinical factors on adherence to topical treatment in psoriasis. (2) Methods: Self-reported measures and weighing the medicines were used to assess adherence. Psychopathological symptoms were measured using the Brief Symptoms Inventory (BSI). Social and clinical factors were assessed by a sociodemographic and clinical questionnaire. Adherence to treatment with topical medication was assessed using a sample of 102 psoriasis patients. (3) Results: The explanatory models of adherence to topical treatment in psoriasis translated into positive associations between adherence and the education level (higher education) (p = 0.03; φ = 0.23), the single-family household (p = 0.01; φ = 0.44), active employment status (p = 0.05; φ = -0.19), familiar history of psoriasis (p = 0.04; φ = -0.21), and the presence of obsessive-compulsive symptoms (p = 0.01; d = 0.29). (4) Conclusions: In patients who present the characteristics identified that influence non-adherence, instructions should be reinforced to increase adherence. The experimental mortality (39.6%) reduced the sample size, representing a limitation of the study.

Ganglioside GD3 Regulates Inflammation and Epithelial-to-Mesenchymal Transition in Human Nasal Epithelial Cells.

Chronic sinusitis with nasal polyps (CRSwNP) is one of the most common chronic inflammatory diseases, and involves tissue remodeling. One of the key mechanisms of tissue remodeling is the epithelial-mesenchymal transition (EMT), which also represents one of the pathophysiological processes of CRS observed in CRSwNP tissues. To date, many transcription factors and forms of extracellular stimulation have been found to regulate the EMT process. However, it is not known whether gangliosides, which are the central molecules of plasma membranes, involved in regulating signal transmission pathways, are involved in the EMT process. Therefore, we aimed to determine the role of gangliosides in the EMT process. First, we confirmed that N-cadherin, which is a known mesenchymal marker, and ganglioside GD3 were specifically expressed in CRSwNP_NP tissues. Subsequently, we investigated whether the administration of TNF-α to human nasal epithelial cells (hNECs) resulted in the upregulation of ganglioside GD3 and its synthesizing enzyme, ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialytransferase 1 (ST8Sia1), and the consequently promoted inflammatory processes. Additionally, the expression of N-cadherin, Zinc finger protein SNAI2 (SLUG), and matrix metallopeptidase 9 (MMP-9) were elevated, but that of E-cadherin, which is known to be epithelial, was reduced. Moreover, the inhibition of ganglioside GD3 expression by the siRNA or exogenous treatment of neuraminidase 3 (NEU 3) led to the suppression of inflammation and EMT. These results suggest that gangliosides may play an important role in prevention and therapy for inflammation and EMT.