scholarly journals Cyclophosphamide Decreases Nitrotyrosine Formation and Inhibits Nitric Oxide Production by Alveolar Macrophages in Mycoplasmosis

2001 ◽  
Vol 69 (10) ◽  
pp. 6401-6410 ◽  
Author(s):  
Judy M. Hickman-Davis ◽  
J. Russell Lindsey ◽  
Sadis Matalon
Keyword(s):  
Nitric Oxide ◽  
Alveolar Macrophages ◽  
Inflammatory Cells ◽  
Lung Lesion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Polymorphonuclear Cells ◽  
Mycoplasmal Infection ◽  
Nitrate And Nitrite

ABSTRACT We previously reported that congenic C57BL/6 inducible nitric oxide synthase−/− (iNOS−/−) mice infected withMycoplasma pulmonis developed higher bacterial numbers and lung lesion scores than C57BL/6 iNOS+/+ controls but had similar lung nitrotyrosine levels. The present studies investigated the role of inflammatory cells in nitrotyrosine formation during mycoplasmal infection. iNOS+/+ and iNOS−/−mice were injected with cyclophosphamide (CYP) and inoculated with 107 CFU of M. pulmonis. CYP pretreatment ofM. pulmonis-infected iNOS+/+ and iNOS−/− mice reduced polymorphonuclear cells (PMNs) within bronchoalveolar lavages (BALs) by 88 and 72%, respectively, and whole-lung myeloperoxidase levels by 80 and 78%, respectively, at 72 h postinfection but did not alter the number of alveolar macrophages (AMs) in BALs. CYP treatment also significantly decreased nitrate and nitrite (NOx) levels in BALs and plasma of infected iNOS+/+ mice, whereas neither CYP nor mycoplasmal infection altered NOx in iNOS−/− mice. CYP reduced lung nitrotyrosine levels in both iNOS+/+ and iNOS−/− mice to uninfected-control levels as shown by immunohistochemical staining and enzyme-linked immunosorbent assay and inhibited mycoplasmal killing by iNOS+/+ mice in vivo. CYP inhibited the production of gamma interferon-inducible NOx by iNOS+/+ AMs in vitro but did not alter the number of iNOS-positive AMs, as detected by immunocytochemistry. In addition, AMs from CYP-treated iNOS+/+ mice had significantly decreased ability to kill mycoplasmas in vitro. These results demonstrate that reactive species generated by inflammatory cells as well as PMN myeloperoxidase are important contributors to nitrotyrosine formation during mycoplasmal infection and that treatment with CYP decreases NO⋅ production by AMs and inhibits mycoplasmal killing.

Ethanol suppresses LPS-induced mRNA for nitric oxide synthase II in alveolar macrophages in vivo and in vitro

Alcohol ◽  
1994 ◽  
Vol 11 (6) ◽  
pp. 539-547 ◽  
Author(s):  
Stanley S. Greenberg ◽  
Jianming Xie ◽  
Ye Wang ◽  
Jay Kolls ◽  
Tadeus Malinski ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Alveolar Macrophages ◽  
Oxide Synthase

scholarly journals L-Theanine Reduced the Development of Knee Osteoarthritis in Rats via Its Anti-Inflammation and Anti-Matrix Degradation Actions: In Vivo and In Vitro Study

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1988 ◽  
Author(s):  
Hui Bai ◽  
Zhiheng Zhang ◽  
Yue Li ◽  
Xiaopeng Song ◽  
Tianwen Ma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Quantitative Polymerase Chain Reaction ◽  
Hydrolytic Enzyme ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matrix Degradation ◽  
In Vivo Animal Model

The etiology of osteoarthritis (OA) is multifactorial, with no effective disease-modifying-drugs. L-theanine has been reported to inhibit inflammatory responses in some diseases and this study aimed to investigate the effect of L-theanine on Interleukin-1(IL-1)β-stimulated chondrocytes, and in an injury-induced OA rat model. Primary chondrocytes were stimulated by IL-1β (10 ng/mL) for 24 h and then co-cultured with L-theanine for 24 h. The effects of L-theanine on IL-1β-stimulated expression of pro-inflammatory cytokines and hydrolytic enzyme were analyzed using Western blotting, quantitative polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. An immunofluorescence assay was used to detect nuclear factor kappa B (NF-κB) phosphorylation. OA was induced by anterior cruciate ligament transection (ACLT) surgery in rats and celecoxib was used as a positive control. OA severity was measured using the Osteoarthritis Research Society International (OARSI) grading system to describe histological changes. The results showed that L-theanine decreased the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), both in vivo and in vitro. L-theanine treatment inhibited IL-1β-induced upregulation of matrix metalloproteinases (MMP)-3 and MMP-13, as well as inhibited NF-κB p65 activation. In vivo animal model showed that L-theanine administration (200 mg/kg) significantly alleviated OA lesions and decreased OARSI score. Our data indicated that L-theanine decreased inflammatory cytokines and protected extracellular matrix degradation through inhibition of the NF-κB pathway, and L-theanine may be considered a promising therapeutic strategy in OA prevention.

scholarly journals In Vivo Blockage of Nitric Oxide with Aminoguanidine Inhibits Immunosuppression Induced by an Attenuated Strain of Salmonella typhimurium, PotentiatesSalmonella Infection, and Inhibits Macrophage and Polymorphonuclear Leukocyte Influx into the Spleen

1999 ◽  
Vol 67 (2) ◽  
pp. 891-898 ◽  
Author(s):  
Amanda Shearer MacFarlane ◽  
Martin G. Schwacha ◽  
Toby K. Eisenstein
Keyword(s):  
Nitric Oxide ◽  
Salmonella Typhimurium ◽  
No Production ◽  
Murine Splenocytes ◽  
Paradoxical Effects ◽  
Leukocyte Influx ◽  
Persistent Bacteremia ◽  
Nitrate And Nitrite

ABSTRACT Our laboratory has previously shown that after immunization with a strain of Salmonella typhimurium, SL3235, made avirulent by a blockage in the pathway of aromatic synthesis, murine splenocytes were profoundly suppressed in their capacity to mount an in vitro antibody plaque-forming cell (PFC) response to sheep erythrocytes. Evidence indicated that suppression was mediated by nitric oxide (NO), since the in vitro addition ofN G-monomethyl-l-arginine blocked suppression. The present studies examined the effect of blocking NO production on Salmonella-induced immunosuppression by in vivo administration of aminoguanidine hemisulfate (AG). AG was administered to C3HeB/FeJ mice in their drinking water (2.5% solution) for 7 days prior to intraperitoneal inoculation with SL3235. AG treatment inhibited the increase in nitrate and nitrite levels in plasma and nitrite levels in the spleen seen in immunized mice. Importantly, AG treatment completely blocked suppression of the splenic PFC response and markedly attenuated the suppression of the response to concanavalin A in immunized mice, providing further evidence thatSalmonella-induced immunosuppression is mediated by NO. AG treatment also alleviated the majority of the splenomegaly associated with SL3235 inoculation, which correlated with a blockage of influx of neutrophils and macrophages into spleens, as assessed by flow cytometry. AG treatment unexpectedly resulted in 90% mortality in mice injected with the highly attenuated vaccine strain ofSalmonella, SL3235. Increased mortality in AG-treated mice correlated with inability to clear organisms from the spleen by day 15 postinoculation and with persistent bacteremia, compared with control mice. Collectively, these in vivo results underscore the dual biological consequences of NO production followingSalmonella infection, with NO being necessary for host defense, but also having the potentially adverse effect of immunosuppression. A unifying hypothesis to explain how these seemingly paradoxical effects could both result from NO production is presented.

scholarly journals Betulin Alleviates the Inflammatory Response in Mouse Chondrocytes and Ameliorates Osteoarthritis via AKT/Nrf2/HO-1/NF-κB Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenghao Ren ◽  
Jie Jin ◽  
Wei Hu ◽  
Qi Chen ◽  
Jian Yang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Joint Disease ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Birch Bark ◽  
Necrosis Factor Alpha ◽  
Collagen Ii ◽  
Cox 2

Osteoarthritis (OA) is a common degenerative joint disease featuring the degeneration, destruction, and ossification of cartilage. Inflammation which may facilitate OA occurrence and development is considered as the main pathological factor. Betulin, a natural product extracted from birch bark, has been commonly used for inflammation treatment; however, its role in OA remains unclear. This study is aimed to explore whether betulin can suppress IL-1β–induced inflammation in chondrocytes and alleviate OA in vitro and in vivo. In in vitro studies, the generation of pro-inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2), and nitric oxide (NO), was assessed using the enzyme-linked immunosorbent assay (ELISA) and Griess reaction. As revealed by results, betulin inhibited the expression of pro-inflammatory mediators. In addition, the protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), matrix metalloproteinase (MMP-13), thrombospondin motifs 5 (ADAMTS5), Collagen II, and Aggrecan were quantified using Western blot analysis. We found that betulin could inhibit the generation of COX-2 and iNOS induced by IL-1β, indicating that betulin has anti-inflammatory effects in chondrocytes. Furthermore, betulin downregulates the expression of MMP-13 and ADAMTS-5 and upregulates the expression of Collagen II and Aggrecan, indicating that it can inhibit the degradation of the extracellular matrix. In mechanism, betulin activated the AKT/Nrf2 pathway and inhibited the phosphorylation of p65. In in vivo studies, administration of betulin in vivo could inhibit cartilage destruction and inflammatory progression. Therefore, these findings suggest that betulin may alleviate IL-1β–induced OA via the AKT/Nrf2/HO-1/NF-κB signal axis, and betulin may be a potential drug for the treatment of OA.

scholarly journals Water Extract of Acori Graminei Rhizoma Attenuates Features of Rheumatoid Arthritis in DBA/1 Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jong-Hyun Nho ◽  
A-Hyeon Kim ◽  
Ho-Kyung Jung ◽  
Mu-Jin Lee ◽  
Ji-Hun Jang ◽  
...  
Keyword(s):  
Liver Toxicity ◽  
Hematological Parameters ◽  
Water Extract ◽  
Inflammatory Cells ◽  
Type Ii Collagen ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type Ii

The dry rhizome of Acorus gramineus Solander, known as Acori Graminei Rhizoma, is used to treat dementia, stroke, eczema, and indigestion in traditional Chinese medicine, traditional Korean medicine, and traditional Japanese Kampo medicine. Previous studies have reported that Acori Graminei Rhizoma extract ameliorated cognitive impairment in Aβ1-42 injected mice. However, the effect of Acori Graminei Rhizoma on type II collagen induced arthritis (CIA) has not been elucidated. Thus, we evaluated the water extract of Acori Graminei Rhizoma (WAG) in CIA mice models. Male DBA/1 mice were separated into five groups (NOR; n=10, CON; n=10, CIA + methotrexate (MTX); n=10, CIA + 100 mg/kg WAG; n=10, CIA + 500 mg/kg WAG; n=10). CIA was induced by injecting the mice with bovine type II collagen, after which the mice were treated with WAG and/or MTX. Hematological parameters and liver and kidney serum toxicity markers were analyzed. Further, serum levels of interleukin (IL)-6, TNF-α, and type II collagen IgG were analyzed via enzyme-linked immunosorbent assay (ELISA). Treatment with 500 mg/kg WAG decreased serum levels of IL-6, TNF-α, and collagen IgG in a CIA model. Moreover, WAG treatment decreased CIA-induced swelling of mouse hind legs, infiltration of inflammatory cells into the synovial membrane, and blood neutrophil levels. WAG administration did not influence hematological parameters or kidneys and liver toxicity markers. WAG may be used to treat arthritis by reducing the inflammation indicators. However, further experiments are required to determine how WAG affects inflammation mechanisms in vitro and in vivo.

scholarly journals Mycobacterium avium Infection of Epithelial Cells Results in Inhibition or Delay in the Release of Interleukin-8 and RANTES

1999 ◽  
Vol 67 (10) ◽  
pp. 5069-5075 ◽  
Author(s):  
Felix J. Sangari ◽  
Mary Petrofsky ◽  
Luiz E. Bermudez
Keyword(s):  
Epithelial Cells ◽  
Mycobacterium Avium ◽  
Intestinal Mucosa ◽  
Inflammatory Cells ◽  
Interleukin 8 ◽  
Cell Culture Supernatant ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ht 29

ABSTRACT Mycobacterium avium is an opportunistic pathogen in AIDS patients, who acquire the infection mainly through the gastrointestinal tract. Previous studies in vitro have shown thatM. avium invades epithelial cells of both intestinal and laryngeal origin. In addition, M. avium enters the intestinal mucosa of healthy mice. Because M. aviuminvasion of the intestinal mucosa in vivo initially is not accompanied by significant influx of inflammatory cells, we sought to determine whether M. avium would trigger chemokine release upon entry into epithelial cells by using HT-29 intestinal and HEp-2 laryngeal epithelial cell lines. Chemokine synthesis was measured both by the presence of specific mRNA and protein secretion in the cell culture supernatant as determined by enzyme-linked immunosorbent assay. Infection of HT-29 intestinal cells with M. avium did not induce the release of interleukin-8 (IL-8) or RANTES for up to 7 days postinfection. However, infection of HEp-2 cells resulted in the release of IL-8 and RANTES at 72 h. Similar findings were observed with other AIDS M. avium isolates belonging to different serovars. Secretion of IL-8 by HEp-2 cells was dependent upon bacterial uptake. In addition, prior infection with M. aviumsuppressed IL-8 production by HT-29 cells infected withSalmonella typhimurium. Our results suggest that M. avium infection of epithelial cells is associated with a delay in IL-8 and RANTES production which, in the case of HT-29, is prolonged up to 1 week. These findings may explain the weak inflammatory response after intestinal mucosa invasion in mice and are probably related with the ability of the bacterium to evade the host’s immune response.

Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Deep Tissue ◽  
Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

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