Neutrophil-Derived COX-2 has a Key Role during Inflammatory Hyperalgesia

Carvalho, Nathalia S.; Lemes, Júlia Borges Paes; Pagliusi, Marco; Machado, Ana Carolina; Malange, Kauê Franco; Pral, Laís Passariello; Fachi, José Luís; Nishijima, Catarine Massucato; Santos, Gilson Gonçalves dos; Tambeli, Cláudia Herrera; Sartori, César Renato; Vinolo, Marco Aurélio Ramirez; Parada, Carlos Amílcar

doi:10.1007/s10753-022-01690-5

Cited by 4 publications

(6 citation statements)

References 49 publications

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“…Injection of 1% carrageenan increased COX-2 expression after 3 hours, according to research conducted by Carvalho et al (2022). This study demonstrated that carrageenan injection with increased concentrations is in line with the increased expression of COX-2, COX-1, and IL-6 in inflammatory cells.…”

Section: Discussionsupporting

confidence: 71%

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Carrageenan-Induced Acute Inflammation on Back-Skin of Mice: Histopathological Features, Number of Inflammatory Cells, and Expression of COX-2, COX-1, and IL-6

Widyarini,

Akrom

et al. 2023

WVJ

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Carrageenan is a sulfated polysaccharide obtained from red seaweed (Rhodophyceae) and can trigger inflammatory activation in both humans and laboratory animals. This study aimed to investigate the expression of cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1), and interleukin-6 (IL-6) and the number of inflammatory cells (neutrophil) involved in a carrageenan-induced acute inflammatory model in the back skin of mice. Paraffin blocks from the back skin of female Swiss mice aged 8 weeks were used in this study. The back-skins of 4 groups of 5 mice in each group were subcutaneously injected with 1%, 2%, and 4% carrageenan powder in 0.9% buffer saline and 0.9% buffer saline as control. Skin samples on paraffin blocks were taken 6 hours after carrageenan injection. Furthermore, paraffin blocks were stained with hematoxylin-eosin (HE) to count the number of inflammatory cells. Immunohistochemistry staining using anti-COX-2, COX-1, and IL-6 antibodies was performed to determine the role of inflammatory mediators. The results showed that the number of inflammatory cells (neutrophils) increased significantly following an increase in carrageenan concentrations. The COX-2, COX-1, and IL-6 expressed by inflammatory cells increased significantly at carrageenan concentrations of 1% to 4%. Histopathological features supported the results obtained from the calculation of the number of inflammatory cells and the expression of COX-2, COX-1, and IL-6. The inflammatory markers consisting of COX-2, COX-1, and IL-6 were expressed on the back skin of mice at 6 hours post-injection with 1% to 4% carrageenan. It can be concluded that carrageenan can be used for an acute inflammatory model of the back skin of a mouse. This inflammation model is intended to facilitate the evaluation or measurement of therapeutic and inflammatory responses when test substances are administered topically or transdermal.

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Section: Discussionsupporting

confidence: 71%

“…An increase in inflammatory cells expressing COX-2 after injection of 1-4% carrageenan might be related to the formation of edema and pain around inflammation. A study by Carvalho et al (2022) reported that neutrophil-derived COX-2 plays an important role in inflammatory pain mediation.…”

Section: Discussionmentioning

confidence: 99%

Carrageenan-Induced Acute Inflammation on Back-Skin of Mice: Histopathological Features, Number of Inflammatory Cells, and Expression of COX-2, COX-1, and IL-6

Widyarini,

Akrom

et al. 2023

WVJ

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“…Cyclooxygenases are essential enzymes in the production of prostaglandins (PGs) from arachidonic acid. While COX-1 is constitutively expressed, COX-2 is activated in injured tissues, resulting in inflammatory processes (Carvalho et al 2022 ). COX-2 inhibition may result in anti-inflammatory effects (Ju et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…This comes in accordance with the observations from other reports (Johnson et al 2020 ). IL-1β induces fibroblast growth, promotes the production of collagenase, and inhibits endothelial cell development, making it an antagonist of extracellular matrix metabolism (Carvalho et al 2022 ). Furthermore, IL-1β has been shown to promote the proliferation of smooth muscle cells and to serve as a chemoattractant for neutrophils and macrophages (Paramel et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Nanosponge hydrogel of octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate of Alcaligenes faecalis

El-Sayed,

Abdelaziz,

El-Housseiny

et al. 2024

Appl Microbiol Biotechnol

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Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate (ODHP) was extracted in a previous study from the culture broth of soil isolate Alcaligenes faecalis MT332429 and showed a promising antimycotic activity. This study was aimed to formulate ODHP loaded β-cyclodextrins (CD) nanosponge (NS) hydrogel (HG) to control skin fungal ailments since nanosponges augment the retention of tested agents in the skin. Box-Behnken design was used to produce the optimized NS formulation, where entrapment efficiency percent (EE%), polydispersity index (PDI), and particle size (PS) were assigned as dependent parameters, while the independent process parameters were polyvinyl alcohol % (w/v %), polymer-linker ratio, homogenization time, and speed. The carbopol 940 hydrogel was then created by incorporating the nanosponges. The hydrogel fit Higuchi’s kinetic release model the best, according to in vitro drug release. Stability and photodegradation studies revealed that the NS-HG remained stable under tested conditions. The formulation also showed higher in vitro antifungal activity against Candida albicans compared to the control fluconazole. In vivo study showed that ODHP-NS-HG increased survival rates, wound contraction, and healing of wound gap and inhibited the inflammation process compared to the other control groups. The histopathological examinations and Masson’s trichrome staining showed improved healing and higher records of collagen deposition. Moreover, the permeability of ODHP-NS-HG was higher through rats’ skin by 1.5-folds compared to the control isoconazole 1%. Therefore, based on these results, NS-HG formulation is a potential carrier for enhanced and improved topical delivery of ODHP. Our study is a pioneering research on the development of a formulation for ODHP produced naturally from soil bacteria. Key points • Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate was successfully formulated as a nanosponge hydrogel and statistically optimized. • The new formula exhibited in vitro good stability, drug release, and higher antifungal activity against C. albicans as compared to the fluconazole. • Ex vivo showed enhanced skin permeability, and in vivo analysis showed high antifungal activity as evidenced by measurement of various biochemical parameters and histopathological examination.

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“…In obese women, vascular inflammation is strongly associated with neutrophil infiltration, and COX-2 staining is highly correlated with the neutrophil marker CD66b staining, suggesting that COX2 may be associated with neutrophil inflammation ( 58 ). During acute inflammation, when neutrophils are exposed to bacterial endotoxins, cytokines, and hormones, they evoke activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB), which in turn promotes the expression of COX-2 and production of PGE2 ( 59 ), which also has a vital role in the regulation of inflammatory nociceptive hypersensitivity ( 60 ). Meanwhile, it has been found that bioactive implants can recruit neutrophils and trigger neutrophil extracellular traps during osseointegration, which are effective in promoting PGE2 production ( 61 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of novel biomarkers related to neutrophilic inflammation in COPD

Huang,

Niu,

Wang

et al. 2024

Front. Immunol.

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BackgroundChronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic respiratory diseases and the fourth cause of mortality globally. Neutrophilic inflammation has a vital role in the occurrence and progression of COPD. This study aimed to identify the novel hub genes involved in neutrophilic inflammation in COPD through bioinformatic prediction and experimental validation.MethodsBoth the single-cell RNA sequencing (scRNA-seq) dataset (GSE173896) and the RNA sequencing (RNA-seq) dataset (GSE57148) were downloaded from the Gene Expression Omnibus (GEO) database. The Seurat package was used for quality control, dimensions reduction, and cell identification of scRNA-seq. The irGSEA package was used for scoring individual cells. The Monocle2 package was used for the trajectory analysis of neutrophils. The CIBERSORT algorithm was used for analysis of immune cell infiltration in the lungs of COPD patients and controls in RNA-seq dataset, and weighted gene co-expression network analysis (WGCNA) correlated gene modules with neutrophil infiltration. The Mendelian randomization (MR) analysis explored the causal relationship between feature DEGs and COPD. The protein–protein interaction (PPI) network of novel hub genes was constructed, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate novel hub genes in clinical specimens.ResultsIn scRNA-seq, the gene sets upregulated in COPD samples were related to the neutrophilic inflammatory response and TNF-α activation of the NF-κB signaling pathway. In RNA-seq, immune infiltration analysis showed neutrophils were upregulated in COPD lung tissue. We combined data from differential and modular genes and identified 51 differential genes associated with neutrophilic inflammation. Using MR analysis, 6 genes were explored to be causally associated with COPD. Meanwhile, 11 hub genes were identified by PPI network analysis, and all of them were upregulated. qRT-PCR experiments validated 9 out of 11 genes in peripheral blood leukocytes of COPD patients. Furthermore, 5 genes negatively correlated with lung function in COPD patients. Finally, a network of transcription factors for NAMPT and PTGS2 was constructed.ConclusionThis study identified nine novel hub genes related to the neutrophilic inflammation in COPD, and two genes were risk factors of COPD, which may serve as potential biomarkers for the clinical severity of COPD.

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Neutrophil-Derived COX-2 has a Key Role during Inflammatory Hyperalgesia

Cited by 4 publications

References 49 publications

Carrageenan-Induced Acute Inflammation on Back-Skin of Mice: Histopathological Features, Number of Inflammatory Cells, and Expression of COX-2, COX-1, and IL-6

Carrageenan-Induced Acute Inflammation on Back-Skin of Mice: Histopathological Features, Number of Inflammatory Cells, and Expression of COX-2, COX-1, and IL-6

Nanosponge hydrogel of octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate of Alcaligenes faecalis

Identification of novel biomarkers related to neutrophilic inflammation in COPD

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