scholarly journals Elevated levels of prostaglandin E2 in the tears of patients with severe allergic conjunctivitis and primary cultured conjunctival cells are suppressed by ketotifen and dexamethasone

2021 ◽  
Vol 6 (1) ◽  
pp. e000571
Author(s):  
Ryutaro Yamanishi ◽  
Naoko Okada ◽  
Eisuke Shimizu ◽  
Hiroshi Fujishima
Keyword(s):  
Allergic Conjunctivitis ◽  
Primary Cultures ◽  
Allergic Inflammation ◽  
Prostaglandin E ◽  
Eye Drops ◽  
Ketotifen Fumarate ◽  
Tnf Α ◽  
Conjunctival Cells ◽  
Culture Supernatants ◽  
Necrosis Factor

ObjectiveWe examined the production of prostaglandin E2 (PGE2), which is the key prostaglandin involved in inflammatory disorders of the ocular surface. Tears and conjunctival fibroblasts were evaluated in order to assess allergic inflammation and the effect of specific drugs.Methods and analysisPGE2 was measured in tears from both patients and normal volunteers. Primary cultures of human conjunctival fibroblasts were incubated with interleukin (IL)-4 and tumour necrosis factor (TNF)-α with or without ketotifen fumarate or dexamethasone. The culture supernatants were removed 24 hours after exposure and the concentrations of PGE2 were quantified by ELISA.ResultsSignificantly higher levels of PGE2 were observed in the tears of patients with severe allergic conjunctivitis than in those with post-surgical inflammation (p=0.02), and this production was reduced by eye drops. Stimulation with IL-4 and TNF-α induced the generation of PGE2 in supernatants of conjunctival fibroblasts, and this production was significantly downregulated by ketotifen fumarate or steroids.ConclusionPGE2 may participate in the pathogenesis of severe ocular allergic disease, and both ketotifen fumarate and steroid reduce the production of PGE2.

scholarly journals Low Expression of IL-10 in Circulating Bregs and Inverted IL-10/TNF-α Ratio in Tears of Patients with Perennial Allergic Conjunctivitis: A Preliminary Study

2019 ◽  
Vol 20 (5) ◽  
pp. 1035 ◽  
Author(s):  
Alberto Salazar ◽  
Israel Casanova-Méndez ◽  
Michele Pacheco-Quito ◽  
Henry Velázquez-Soto ◽  
Julio Ayala-Balboa ◽  
...  
Keyword(s):  
Allergic Conjunctivitis ◽  
Allergic Diseases ◽  
Healthy Controls ◽  
The Novel ◽  
Inflammatory Microenvironment ◽  
Tnf Α ◽  
The Mean ◽  
Preliminary Study ◽  
Necrosis Factor ◽  
Low Expression

Allergic conjunctivitis (AC) is one of the most common ophthalmological disorders seen in clinical practice. Growing evidence from recent years suggests that a subset of IL-10-expressing B cells is involved in inflammatory allergic diseases. In this study, we aimed to evaluate the potential involvement of blood Bregs cells in perennial allergic conjunctivitis (PAC), and interleukins (IL)-1β, IL-6, IL-8, IL-10, and IL-12, and tumor necrosis factor (TNF)-α, were measured in tear samples and compared with healthy controls (HC) using flow cytometry. Non-significant differences in CD19+IL-10+ cell frequency between PAC patients and healthy controls (HC) were observed. Nevertheless, when we analyzed the mean fluorescence intensity (MFI) of IL-10 on CD19+CD38Lo/Med/Hi-gated cells, we observed a significant decrease in MFI in all Bregs subsets in PAC patients. Additionally, tear cytokines showed 2.8 times lower levels of IL-10 than TNF-α in PAC patients when compared to HC. Our findings demonstrate an immunological dysregulation in patients with allergic conjunctivitis, characterized by the low expression of IL-10 in circulating CD19+CD38+ Bregs subsets and an inverted tear IL-10/TNF-α ratio, promoting a local pro-inflammatory microenvironment. These findings highlight the novel pathologic changes involved in ocular allergic diseases. Understanding systemic and local mechanisms will aid the design of immunomodulating therapeutics at different levels.

Bortezomib Therapy in Patients With Relapsed or Refractory Lymphoma: Potential Correlation of In Vitro Sensitivity and Tumor Necrosis Factor Alpha Response With Clinical Activity

2006 ◽  
Vol 24 (13) ◽  
pp. 2105-2112 ◽  
Author(s):  
Sandra J. Strauss ◽  
Lenushka Maharaj ◽  
Susan Hoare ◽  
Peter W. Johnson ◽  
John A. Radford ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Cell Lymphoma ◽  
Primary Cultures ◽  
Necrosis Factor Alpha ◽  
In Vitro Sensitivity ◽  
Tnf Α ◽  
Heavily Pretreated ◽  
Factor Alpha ◽  
Necrosis Factor

Purpose To determine the efficacy of bortezomib in patients with lymphoid malignancy, correlating clinical response with effect on plasma cytokines and in vitro activity in primary cultures. Patients and Methods Patients received bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11 of a 3-week cycle. Plasma tumor necrosis factor alpha (TNF-α) and interleukin-6 were measured before each treatment, and bortezomib activity was examined in patient samples grown in primary culture. Results Fifty-one patients received a total of 193 cycles of treatment. Twenty-four patients had mantle cell lymphoma (MCL), 13 had follicular lymphoma (FL), six had lymphoplasmacytic lymphoma, six had Hodgkin's disease (HD), and one each had diffuse large B-cell lymphoma and adult T-cell leukemia/lymphoma. Patients were heavily pretreated with a median of four previous therapies. Significant grade 3 to 4 toxicities were thrombocytopenia (n = 22), fatigue (n = 10), and peripheral neuropathy (n = 3). Seven patients with MCL responded to treatment (one complete response, six partial responses [PRs]; overall response rate, 29%). Two patients with FL achieved a late PR 3 months after discontinuing therapy. Two patients with Waldenström's macroglobulinemia and one patient with HD achieved a PR. MCL primary cultures demonstrated greater sensitivity to bortezomib than FL (median 50% effective concentration for viability, 209 nmol/L v 1,311 nmol/L, respectively; P = .07), which correlated with clinical response. A median reduction in plasma TNF-α of 98% was observed in six patients with MCL who responded to bortezomib compared with a reduction of 38% in six nonresponders (P = .07). Conclusion Bortezomib demonstrates encouraging efficacy in MCL in heavily pretreated individuals. Response was associated with a reduction in plasma TNF-α and in vitro sensitivity in a small number of patients.

scholarly journals Cytokine Synthesis by Chondroblastoma: Relation to Local Inflammation

2009 ◽  
Vol 17 (1) ◽  
pp. 56-61 ◽  
Author(s):  
C Uchikawa ◽  
T Shinozaki ◽  
T Nakajima ◽  
K Takagishi
Keyword(s):  
Tumour Necrosis ◽  
Cytokine Production ◽  
Giant Cell Tumour ◽  
Prostaglandin E ◽  
Local Inflammation ◽  
Tnf Α ◽  
Cytokine Synthesis ◽  
Joint Arthritis ◽  
Necrosis Factor ◽  
Immunohistochemical Analyses

Purpose. To investigate cytokine production by chondroblastoma in inducing local inflammation and adjacent-joint arthritis. Methods. Immunohistochemical analyses of curetted tissues using anti-human interleukin (IL)-1β, IL-6, IL-8, and tumour necrosis factor (TNF)-α were performed for 6 patients with chondroblastoma and 3 patients with giant cell tumour (GCT) of bone. In addition, prostaglandin E2, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, and TNF-α in the cyst fluid of one of the patients with chondroblastoma and 2 with GCT of bone were measured using immunoassay kits. Conclusion. Cytokines such as IL-1β, IL-8, TNF-α, and particularly IL-6 play an important role in local inflammation in patients with chondroblastoma.

scholarly journals PKCϵ is involved in JNK activation that mediates LPS-induced TNF-α, which induces apoptosis in macrophages

2003 ◽  
Vol 285 (5) ◽  
pp. C1235-C1245 ◽  
Author(s):  
Mònica Comalada ◽  
Jordi Xaus ◽  
Annabel F. Valledor ◽  
Carlos López-López ◽  
Daniel J. Pennington ◽  
...  
Keyword(s):  
Cell Model ◽  
Primary Cultures ◽  
Signaling Mechanism ◽  
Major Function ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Jnk Activation ◽  
Necrosis Factor

Lipopolysaccharide (LPS) is a powerful stimulator of macrophages and induces apoptosis in these cells. Using primary cultures of bone marrow-derived macrophages, we found that the autocrine production of tumor necrosis factor-α (TNF-α) has a major function in LPS-induced apoptosis. LPS activates PKC and regulates the different mitogen-activated protein kinases (MAPK). We aimed to determine its involvement either in the secretion of TNF-α or in the induction of apoptosis. Using specific inhibitors and mice with the gene for PKCϵ disrupted, we found that LPS-induced TNF-α-dependent apoptosis is mostly mediated by PKCϵ, which is not directly involved in the signaling mechanism of apoptosis but rather in the process of TNF-α secretion. In our cell model, all three MAPKs were involved in the regulation of TNF-α secretion, but at different levels. JNK mainly regulates TNF-α transcription and apoptosis, whereas ERK and p38 contribute to the regulation of TNF-α production, probably through posttranscriptional mechanisms. Only JNK activity is mediated by PKCϵ in response to LPS and so plays a major role in TNF-α secretion and LPS-induced apoptosis. We demonstrated in macrophages that LPS involving PKCϵ regulates JNK activity and produces TNF-α, which induces apoptosis.

scholarly journals A Novel, Tumor-Induced Osteoclastogenesis Pathway Insensitive to Denosumab but Interfered by Cannabidiol

2019 ◽  
Vol 20 (24) ◽  
pp. 6211
Author(s):  
Maiko Tsuchiya ◽  
Kou Kayamori ◽  
Akane Wada ◽  
Motohiro Komaki ◽  
Yae Ohata ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Metabolism ◽  
Nuclear Factor ◽  
Necrosis Factor Alpha ◽  
Local Bone ◽  
Tnf Α ◽  
Psychotropic Effects ◽  
Factor Alpha ◽  
Culture Supernatants ◽  
Necrosis Factor

Bone metabolism is strictly regulated, and impaired regulation caused by hormonal imbalances induces systemic bone loss. Local bone loss caused by tumor invasion into bone is suggested to be induced by the generation of cytokines, which affect bone metabolism, by tumor cells. The major cause of systemic and local bone losses is excess bone resorption by osteoclasts, which differentiate from macrophages by receptor activator of nuclear factor kappa-B ligand (RANKL) or tumor necrosis factor-alpha (TNF-α). We previously found a novel pathway for tumor-induced osteoclastogenesis targeting osteoclast precursor cells (OPCs). Tumor-induced osteoclastogenesis was resistant to RANKL and TNF-α inhibitors. In the present study, we confirmed that exosomes derived from oral squamous cell carcinoma (OSCC) cells induced osteoclasts from OPCs. We also showed that the depletion of exosomes from culture supernatants of OSCC cells partially interfered with osteoclastogenesis, and cannabidiol, an innoxious cannabinoid without psychotropic effects, almost completely suppressed tumor-induced osteoclastogenesis. Osteoclastogenesis and its interference by cannabidiol were independent of the expression of nuclear factor of T cell c1 (NFATc1). These results show that osteoclastogenesis induced by OSCC cells targeting OPCs is a novel osteoclastogenic pathway independent of NFATc1 expression that is partially caused by tumor-derived exosomes and suppressed by cannabidiol.

scholarly journals Candida albicans-Derived β-1,2-Linked Mannooligosaccharides Induce Desensitization of Macrophages

2000 ◽  
Vol 68 (2) ◽  
pp. 965-968 ◽  
Author(s):  
Thierry Jouault ◽  
Chantal Fradin ◽  
Pierre-André Trinel ◽  
Daniel Poulain
Keyword(s):  
Signal Transduction ◽  
Candida Albicans ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
No Release ◽  
Factor Alpha ◽  
Culture Supernatants ◽  
Arachidonic Acid Derivatives ◽  
Necrosis Factor

ABSTRACT Candida albicans β-1,2-oligomannosides stimulate macrophage tumor necrosis factor alpha (TNF-α) but not NO release. This stimulation desensitized macrophages by altering β-1,2-oligomannoside-dependent TNF-α production and lipopolysaccharide-dependent TNF-α and NO secretion. Desensitization was not related to tyrosine phosphorylation signal transduction but was transferred by culture supernatants in which arachidonic acid derivatives were evidenced.

IL-6 is essential in TNF-α-induced fever

1998 ◽  
Vol 275 (6) ◽  
pp. R2028-R2034 ◽  
Author(s):  
Anna K. Sundgren-Andersson ◽  
Pernilla Östlund ◽  
Tamas Bartfai
Keyword(s):  
Tumor Necrosis ◽  
Prostaglandin E ◽  
High Dose ◽  
Central Administration ◽  
Wild Type ◽  
Febrile Response ◽  
Tnf Α ◽  
Factor Α ◽  
Deficient Mice ◽  
Necrosis Factor

Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine that orchestrates an array of local and systemic effects. For instance, acute exposure to a high dose of TNF-α results in septic shock and fever. We have used interleukin-1β (IL-1β)- and interleukin-6 (IL-6)-deficient mice, along with their wild-type equivalents, to define a role for TNF-α in fever. Briefly, the mice produced prostaglandin E2-dependent fevers in response to recombinant murine TNF-α (rmTNF-α). Furthermore, rmTNF-α (12 μg/mouse ip) triggered a febrile response in IL-1β-deficient mice as well as in their corresponding wild-type controls. In contrast, the IL-6-deficient mice were resistant to rmTNF-α (4.5 μg/mouse ip), although their wild-type counterparts readily mounted a fever. In the IL-6-deficient mice, moreover, the febrile response to rmTNF-α could be restored by a central administration of rat recombinant IL-6 (500 ng/mouse icv). We thus conclude that TNF-α can trigger fever independent of IL-1β but dependent on IL-6. We also suggest that central, rather than peripheral, IL-6 (plasma IL-6 was measured 2 h after pyrogenic challenge) is essential in TNF-α-induced fever.

scholarly journals Differential regulation of the release of tumor necrosis factor-α and of eicosanoids by mast cells in rat airways after antigen challenge

2003 ◽  
Vol 12 (4) ◽  
pp. 237-246 ◽  
Author(s):  
Aryene Goes Trezena ◽  
Zilma Lucia da Silva ◽  
Ricardo Martins Oliveira-filho ◽  
Amilcar Sabino Damazo ◽  
Anita Hilda Straus ◽  
...  
Keyword(s):  
Mast Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Prostaglandin E ◽  
Tnf Α ◽  
Topographical Distribution ◽  
Factor Α ◽  
Rat Trachea ◽  
Necrosis Factor

Background:Rat trachea display a differential topographical distribution of connective tissue mast cells (CTMC) and mucosal mast cells (MMC) that may imply regional differences in the release of allergic mediators such as tumor necrosis factor-α (TNF-α) and eicosanoids.Aim:To evaluate the role of CTMC and MMC for release of TNF-α and eicosanoids after allergenic challenge in distinct segments of rat trachea.Materials and methods:Proximal trachea (PT) and distal trachea (DT) from ovalbumin (OVA)-sensitized rats, treated or not with compound 48/80 (48/80) or dexamethasone, were incubated in culture medium. After OVA challenge, aliquots were collected to study release of TNF-α and eicosanoids.Results:Release of TNF-α by PT upon OVA challenge peaked at 90 min and decayed at 6 and 24 h. Release from DT peaked at 30-90 min and decayed 6 and 24 h later. When CTMC were depleted with 48/80, OVA challenge exacerbated the TNF-α release by PT at all time intervals, while DT exacerbated TNF-α levels 6 and 24 h later only. Dexamethasone reduced TNF-α production after 90 min of OVA challenge in PT and at 3 and 6h in DT. OVA challenge increased prostaglandin D2in DT and leukotriene B4in both segments but did not modify prostaglandin E2and leukotriene C4release.Conclusion:OVA challenge induces TNF-α release from MMC, which is negatively regulated by CTMC. The profile of TNF-α and eicosanoids depends on the time after OVA challenge and of the tracheal segment considered.

Sign in / Sign up

Export Citation Format

Share Document