ASB16165, a phosphodiesterase 7A inhibitor, reduces cutaneous TNF-α level and ameliorates skin edema in phorbol ester 12-O-tetradecanoylphorbol-13-acetate-induced skin inflammation model in mice

Актуальность. Фактор некроза опухоли(TNF-α) является провоспалительным цитокином, продуцирующимся макрофагами и многими другими клетками. Данные о вариации концентрацииTNF-α во влаге передней камеры глаза у лиц, не имеющих выраженных воспалительных и аутоиммунных процессов практически единичны. Цель. Исследование диапазона вариации фактора некроза опухоли альфа во влаге передней камеры глаза у пациентов с возрастной катарактой. Материал и методы. Отобраны и обследованы 33 пациента, в возрасте от 47 до 82 лет, госпитализированных для плановой экстракции катаракты не имеющих выраженных сопутствующих воспалительных заболеваний (аутоиммунных, острых инфекционных болезней, обострением хронических заболеваний, глаукомы, перенесенного увеита и др.). Влага передней камеры забиралась при вскрытии передней камеры глаза во время факоэмульсификации катаракты. Исследование TNF-αпроводилось с помощью иммуноферментны хтест-систем, разработанных при участии сотрудников кафедры клинической иммунологии, аллергологии и эндокринологии ГОО ВПО «ДонНМУ им.М. Горького». Вышеуказанные тест-системы характеризует высокая чувствительность (0,5 пикограмм в миллилитре) и хорошая воспроизводимость. Результаты. При исследовании уровня TNF-αво влаге передней камеры глаза у пациентов с возрастной катарактой, мы выявили колебания данного показателя от 0 до 2,49 пкг/мл. Следует отметить, что полученные нами результаты показывают небольшую вариацию (в пределах низких значений) данного провоспалительного цитокина в исследованной жидкости у пациентов в возрасте от 47 до80 лет, не имеющих выраженной воспалительной(аутоиммунной и др.) патологии. Выводы. Показана низкая вариация TNF-α во влаге передней камеры глаза у пациентов с возрастной катарактой (у обследуемых исключена сопутствующая выраженная воспалительная патология). Результаты можно также использовать как контрольные при проведении сравнительныхисследований этого цитокина в данной среде у лицс различными заболеваниями глаза.

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Cortistatin Dampens Psoriasis-Like Skin Inflammation Through Interacting with TNF-Α/TNFR1/Nf-κB Signaling Pathway and Regulating Macrophage Polarization

SSRN Electronic Journal ◽

10.2139/ssrn.3501018 ◽

2019 ◽

Author(s):

Wenhan Wang ◽

Yunpeng Zhao ◽

Chao Liu ◽

Cheng Qiu ◽

Jiayi Li ◽

...

Keyword(s):

Signaling Pathway ◽

Macrophage Polarization ◽

Skin Inflammation ◽

Tnf Α

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TNF-α Suppresses Autophagic Flux in Acinar Cells in IgG4-Related Sialadenitis

Journal of Dental Research ◽

10.1177/0022034519871890 ◽

2019 ◽

Vol 98 (12) ◽

pp. 1386-1396 ◽

Cited By ~ 3

Author(s):

X. Hong ◽

S.N. Min ◽

Y.Y. Zhang ◽

Y.T. Lin ◽

F. Wang ◽

...

Keyword(s):

Acinar Cell ◽

Cell Injury ◽

Ex Vivo ◽

Secretory Granules ◽

Acinar Cells ◽

Autophagic Flux ◽

C6 Cells ◽

Tnf Α ◽

Α Level

IgG4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic fibroinflammatory disease that affects salivary glands and leads to hyposalivation. Tumor necrosis factor–α (TNF-α) is a critical proinflammatory cytokine involved in several salivary gland disorders, but its role and mechanism regarding acinar cell injury in IgG4-RS are unknown. Here, we found that TNF-α level was significantly increased in serum and submandibular gland (SMG) of patients and that serum TNF-α level was negatively correlated with saliva flow rate. Ultrastructural observations of IgG4-RS SMGs revealed accumulation of large autophagic vacuoles, as well as dense fibrous bundles, decreased secretory granules, widened intercellular spaces, swollen mitochondria, and expanded endoplasmic reticulum. Expression levels of LC3 and p62 were both increased in patients’ SMGs. TNF-α treatment led to elevated levels of LC3II and p62 in both SMG-C6 cells and cultured human SMG tissues but did not further increase their levels when combined with bafilomycin A1 treatment. Moreover, transfection of Ad-mCherry-GFP-LC3B in SMG-C6 cells confirmed the suppression of autophagic flux after TNF-α treatment. Immunofluorescence imaging revealed that costaining of LC3 and the lysosomal marker LAMP2 was significantly decreased in patients, TNF-α–treated SMG-C6 cells, and cultured human SMGs, indicating a reduction in autophagosome-lysosome fusion. Furthermore, the ratio of pro/mature cathepsin D was elevated in vivo, ex vivo, and in vitro. TNF-α also appeared to induce abnormal acidification of lysosomes in acinar cells, as assessed by lysosomal pH and LysoTracker DND-26 fluorescence intensity. In addition, TNF-α treatment induced transcription factor EB (TFEB) redistribution in SMG-C6 cells, which was consistent with the changes observed in IgG4-RS patients. TNF-α increased the phosphorylation of extracellular signal–regulated kinase (ERK) 1/2, and inhibition of ERK1/2 by U0126 reversed TNF-α–induced TFEB redistribution, lysosomal dysfunction, and autophagic flux suppression. These findings suggest that TNF-α is a key cytokine related to acinar cell injury in IgG4-RS through ERK1/2-mediated autophagic flux suppression.

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High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection

Life ◽

10.3390/life11060527 ◽

2021 ◽

Vol 11 (6) ◽

pp. 527

Author(s):

Lucero A. Ramon-Luing ◽

Ranferi Ocaña-Guzman ◽

Norma A. Téllez-Navarrete ◽

Mario Preciado-García ◽

Dámaris P. Romero-Rodríguez ◽

...

Keyword(s):

Immune Reconstitution Inflammatory Syndrome ◽

Immune Reconstitution ◽

Control Group ◽

Hiv Patients ◽

Art Initiation ◽

Tnf Α ◽

Ifn Γ ◽

Α Level ◽

Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.

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Development and Evaluation of a Topical Anti-Inflammatory Preparation Containing Dodonaea polyandra Extract

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j38p57 ◽

2015 ◽

Vol 18 (4) ◽

pp. 578 ◽

Cited By ~ 4

Author(s):

Bradley S Simpson ◽

Xianling Luo ◽

Jiping Wang ◽

Yunmei Song ◽

David Claudie ◽

...

Keyword(s):

Phase Separation ◽

Human Skin ◽

Dosage Form ◽

Interleukin 1 ◽

In Vitro Release ◽

Skin Inflammation ◽

Skin Model ◽

Inflammation Model ◽

Anti Inflammatory

Purpose: We have previously reported that the Australian Northern Kaanju (Kuuku I’yu) medicinal plant Dodonaea polyandra has anti-inflammatory activity. This is attributed largely to the presence of clerodane diterpenoids contained within the leaf resin. We envisaged developing a topical preparation to treat indications relating to skin inflammation. However, it was unknown whether the resin could be incorporated into a suitable dosage form while retaining the therapeutic value demonstrated in previous work. Therefore, the following study was undertaken to assess parameters of safety and efficacy for a prototype formulation containing the leaf resin extracted from D. polyandra. Methods: Using the assessment criteria of optimum appearance, tactile feeling, spreadability and odour, 78 different formulations were developed. Formulation stability was assessed using a centrifugal test with preparations displaying phase separation further modified or re-formulated. A prototype formulation containing 5% w/w plant resin was selected and subjected to in vitro release studies. This was quantified through HPLC analysis using two major bioactive diterpenoids as reference. The prototype formulation was tested for efficacy in a TPA-induced acute murine skin inflammation model as well as a 3D human skin model for irritancy/toxicity (Epiderm™). Results: The prototype resin cream was a chartreuse-coloured homogenous semisolid preparation that was readily spreadable upon contact with skin with no sensation of tackiness, residual greasiness, or irritation. The optimized cream showed no phase separation after 30 min centrifugation at 825 g. In the TPA-induced inflammation model, the resin formulation significantly reduced ear thickness and interleukin-1 beta levels in mouse ear tissue. The 5% w/w resin cream formulation showed no irritancy in a 3D human skin model. Conclusions: Our results demonstrate that bioactive resin from D. polyandra can be formulated into a stable and non-irritant semi-solid dosage form and reduce parameters of acute skin inflammation in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Diarylheptanoid, a constituent isolated from methanol extract of Alpinia officinarum attenuates TNF-α level in Freund's complete adjuvant-induced arthritis in rats

Journal of Ethnopharmacology ◽

10.1016/j.jep.2018.10.019 ◽

2019 ◽

Vol 229 ◽

pp. 233-245 ◽

Cited By ~ 4

Author(s):

Varsha S. Honmore ◽

Amit D. Kandhare ◽

Parag P. Kadam ◽

Vijay M. Khedkar ◽

Arun D. Natu ◽

...

Keyword(s):

Methanol Extract ◽

Freund’S Complete Adjuvant ◽

Adjuvant Induced Arthritis ◽

Alpinia Officinarum ◽

Freund's Complete Adjuvant ◽

Tnf Α ◽

Α Level

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Anti-inflammatory effects of Anredera cordifolia and Piper crocatum extracts on lipopolysaccharide-stimulated macrophage cell line

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v12i1.28714 ◽

2017 ◽

Vol 12 (1) ◽

pp. 35 ◽

Cited By ~ 7

Author(s):

Dian Ratih Laksmitawati ◽

Anisa Widyastuti ◽

Nadia Karami ◽

Ervi Afifah ◽

Dwi Davidson Rihibiha ◽

...

Keyword(s):

Cell Line ◽

Tumor Necrosis ◽

Macrophage Cell Line ◽

Macrophage Cell ◽

Cell Viability Assay ◽

Viability Assay ◽

Tnf Α ◽

Anti Inflammatory ◽

Α Level ◽

Necrosis Factor

In this study, the anti-inflammatory potential of Anredera cordifolia and Piper crocatum extracts on lipopolysaccharide-induced murine macrophage cell line (RAW 264.7) was observed. Cell viability assay was performed with MTS assay. Parameters measured to determine the anti-inflammatory activity were interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, nitric oxide (NO) and IL-6. Both A. cordifolia and P. crocatum at concentration of 50 µg/mL in cell line resulted significant decrease in TNF-α level (250.3 and 242.5 pg/mL respectively). A. cordifolia showed significant decrease in IL-1β level at 50 µg/mL and IL-6 level at 10 µg/mL, whilst P. crocatum showed significant decrease IL-1β level in three concentrations with lowest level at 50 µg/mL. A. cordifolia showed lowest decrease in NO level at 50 µg/mL but not comparable with normal cells, whilst P. crocatum showed significant decrease in NO level at 50 µg/mL. This research revealed that A. cordifolia and P. crocatum possess the anti-inflammatory potential indicated by the inhibitory activity of the inflammatory mediators including, TNF-α, IL-1β, IL-6, and NO.

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