scholarly journals Recombinant Measles AIK-C Vaccine Strain Expressing Influenza HA Protein

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 149
Author(s):  
Takashi Ito ◽  
Takuji Kumagai ◽  
Yoshiaki Yamaji ◽  
Akihito Sawada ◽  
Tetsuo Nakayama
Keyword(s):  
Influenza A ◽  
Inflammatory Cells ◽  
Alveolar Wall ◽  
Viral Loads ◽  
Empty Vector ◽  
Influenza Hemagglutinin ◽  
Tnf Α ◽  
Cotton Rats ◽  
Ifn Γ ◽  
Ha Protein

Recombinant measles AIK-C vaccine expressing the hemagglutinin (HA) protein of influenza A/Sapporo/107/2013(H1N1pdm) (MVAIK/PdmHA) was constructed. Measles particle agglutination (PA) and influenza hemagglutinin inhibition (HI) antibodies were induced in cotton rats immunized with MVAIK/PdmHA. Cotton rats immunized with two doses of the HA split vaccine were used as positive controls, and higher HI antibodies were detected 3 weeks after the first dose. Following the challenge of A/California/07/2009(H1N1pdm), higher viral loads (107 TCID50/g) were detected in the lung homogenates of cotton rats immunized with the empty vector (MVAIK) or control groups than those immunized with MVAIK/Pdm HA (103 TCID50/g) or the group immunized with HA split vaccine (105 TCID50/g). Histopathologically, destruction of the alveolar structure, swelling of broncho-epithelial cells, and thickening of the alveolar wall with infiltration of inflammatory cells and HA antigens were detected in lung tissues obtained from non-immunized rats and those immunized with the empty vector after the challenge, but not in those immunized with the HA spilt or MVAIK/PdmHA vaccine. Lower levels of IFN-α, IL-1β, and TNF-α mRNA, and higher levels of IFN-γ mRNA were found in the lung homogenates of the MVAIK/PdmHA group. Higher levels of IFN-γ mRNA were detected in spleen cell culture from the MVAIK/PdmHA group stimulated with UV-inactivated A/California/07/2009(H1N1pdm). In conclusion, the recombinant MVAIK vaccine expressing influenza HA protein induced protective immune responses in cotton rats.

scholarly journals Higher Viral Load and Prolonged Viral Shedding Period is Associated with Impaired Th17 Cell Response in Patients with H1N1 Influenza A

2012 ◽  
Vol 1 (3) ◽  
pp. 137-145
Author(s):  
Gui-lin Yang ◽  
Ying-xia Liu ◽  
Mu-tong Fang ◽  
Wei-long Liu ◽  
Xin-chun Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Load ◽  
Cell Response ◽  
Th17 Cell ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Cell Frequency ◽  
Viral Loads ◽  
Viral Shedding ◽  
Ifn Γ

Abstract Objective To explore whether age, disease severity, cytokines and lymphocytes in H1N1 influenza A patients correlate with viral load and clearance. Methods Total of 70 mild and 16 severe patients infected with H1N1 influenza A virus were enrolled in this study. Results It was found that the patients under 14 years old and severe patients displayed significantly higher viral loads and prolonged viral shedding periods compared with the patients over 14 years old and mild patients, respectively (P < 0.05). Moreover, the patients under 14 years old and severe patients displayed significantly lower Th17 cell frequency than the patients over 14 years old and mild patients (P < 0.01). The viral shedding period inversely correlated with the frequency of IL-17+IFN-γ-CD4+ T cells. Additionally, the decreased concentration of serum TGF-β correlated with the decreased frequency of IL-17+IFN-γ-CD4+ T cells. Conclusions Both younger and severe patients are associated with higher viral loads and longer viral shedding periods, which may partially be attributed to the impaired Th17 cell response.

Therapeutic efficacy of Hypericum perforatum L. extract for mice infected with an influenza A virus

2012 ◽  
Vol 90 (2) ◽  
pp. 123-130 ◽  
Author(s):  
Pu Xiuying ◽  
Liang Jianping ◽  
Shang Ruofeng ◽  
Zhou Liye ◽  
Wang Xuehong ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Lung Tissue ◽  
Post Infection ◽  
Therapeutic Efficacy ◽  
Influenza A ◽  
Hypericum Perforatum ◽  
Viral Titer ◽  
Tnf Α ◽  
Hypericum Perforatum L ◽  
Ifn Γ

Hypericum perforatum L., a plant used in Chinese herbal medicine, has been proven effective against many viral diseases. In the present study, the therapeutic efficacy of an extract of H. perforatum (HPE) against influenza A virus (IAV) was investigated in mice. Whether HPE would be a promising agent for influenza treatment was evaluated by measuring the protection rate, mean survival days, lung index, and viral titer, as well as the secretion of IL-6, interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α), and interferon-gamma (IFN-γ) in lung tissue and serum on days 3 and 5 post-infection. The results showed that HPE could reduce the lung index and viral titer of mice infected with IAV, decrease mortality, and prolong the mean survival time. HPE decreased the concentration of IL-6 and TNF-α in lung tissue and serum on day 5 post-infection. In contrast, HPE enhanced the lung and serum levels of IL-10 and IFN-γ on the days 3 and 5 post-infection. Our study indicates that HPE has significant therapeutic efficacy for mice infected with IAV. The possible reasons for these results were concluded to be pertaining to up-regulating the expression of IL-10 and IFN-γ, and down-regulating the secretion of IL-6 and TNF-α in lung and serum.

scholarly journals Interferon γ induces differential upregulation of α and β chemokine secretion in colonic epithelial cell lines

Gut ◽  
1998 ◽  
Vol 42 (2) ◽  
pp. 208-213 ◽  
Author(s):  
A C Warhurst ◽  
S J Hopkins ◽  
G Warhurst
Keyword(s):  
Cell Lines ◽  
Inflammatory Cells ◽  
Interferon Γ ◽  
Inflammatory Protein ◽  
Chemotactic Protein ◽  
Tnf Α ◽  
Activated T Lymphocytes ◽  
Ifn Γ ◽  
Significant Expression ◽  
Factor Α

Background—Production of chemoattractant factors by the intestinal epithelium may contribute to mucosal infiltration by inflammatory cells in inflammatory bowel disease. Secretion of the α chemokine interleukin 8 (IL-8), a neutrophil chemoattractant, has been widely studied, but little is known about epithelial secretion of β chemokines, which are preferentially involved in recruiting monocytes.Aims—To investigate the profiles of α and β chemokine secretion in colonic cell lines and their differential modulation by interferon γ (IFN-γ), a product of activated T lymphocytes and natural killer cells.Methods and results—HT29-19A, a model of the Cl− secretory crypt cell, exhibited a parallel secretion of the α chemokines IL-8 and GROα, which could be markedly upregulated by tumour necrosis factor α (TNF-α) and IL-1β. These cells showed no significant expression of the β chemokines RANTES (regulated upon activation T cell expressed and secreted), MIP-1α (macrophage inflammatory protein 1α), and MCP-1 (monocyte chemotactic protein 1) under these conditions, but IFN-γ in combination with TNF-α caused a dose dependent induction of RANTES and MCP-1 secretion. This was accompanied by a marked increase of RANTES mRNA. In contrast, IFN-γ had no significant effect on TNF-α stimulated IL-8 secretion. Caco-2 cells, with features more typical of villus absorptive cells, were relatively poor secretors of α chemokines but secreted high levels of MCP-1 in response to IL-1β. IFN-γ did not influence α or β chemokine secretion in these cells.Conclusions—These studies suggest that intestinal epithelial cells may produce chemokines capable of attracting both neutrophils and monocytes. The ability of IFN-γ to activate the expression of β chemokines preferentially could facilitate the development of chronic inflammatory infiltrates.

scholarly journals Inhibitory Effect of Sulfated Polysaccharide from Codium edule P.C. Silva Against 2,4-Dinitrofluorobenzene (DNFB)- Induced Allergic Contact Dermatitis on Female BALB/c Mice

2021 ◽  
Author(s):  
Martin Raemond Brondial Mallabo ◽  
Mary Jho - Anne T. Corpuz ◽  
Reginald B. Salonga ◽  
Ross D. Vasquez
Keyword(s):  
Contact Dermatitis ◽  
Allergic Contact Dermatitis ◽  
Inflammatory Cells ◽  
Sulfated Polysaccharide ◽  
Gel Chromatography ◽  
Dependent Manner ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Allergic Contact

Purpose: Sulfated polysaccharide (SP) from Codium species has been reported for its anti-inflammatory activities. However, the effect of SP from C. edule on allergic responses has not been studied. The study was conducted to determine the effect of SP (F1) from C. edule on allergic contact dermatitis (ACD) induced by 2,4-dinitrofluorobenzene (DNFB) in female BALB/c mice. Methods: F1 was isolated using DEAE Sepharose Gel Chromatography and chemically identified by LC-MS analyses. The effects of F1 on changes in ear thickness, allergic responses, and histology were evaluated. The effects of F1 on the production of inflammatory cytokines IFN- γ and TNF-α in serum were also quantified and compared with standard prednisolone therapy. Results: F1 was identified as a heteropolysaccharide with β-D-galactans and β-L-arabinans units. F1 was non-toxic at 2000 mg/kg. Administration of F1 in DNFB-challenged mice significantly suppressed the increase in ear thickness, erythema, desquamation, and proliferation of inflammatory cells. F1 significantly decreased the production of inflammatory markers, IFN- γ and TNF-α in a dose-dependent manner when compared to the untreated group (p<0.05). Conclusion: Results suggest that F1 from C. edule is a bioactive sulfated heteropolysaccharide with anti-inflammatory activity and might be a valuable candidate molecule for the treatment of allergic diseases such as ACD.

scholarly journals Qingwenzhike Prescription Alleviates Acute Lung Injury Induced by LPS via Inhibiting TLR4/NF-kB Pathway and NLRP3 Inflammasome Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Cai Zhang ◽  
Xinran Wang ◽  
Chunguo Wang ◽  
Cheng He ◽  
Quantao Ma ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Inflammasome Activation ◽  
Chemical Compositions ◽  
Alveolar Wall ◽  
Protective Effects ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Underlying Mechanisms

Background: Acute lung injury (ALI) is characterized by dysfunction of the alveolar epithelial membrane caused by acute inflammation and tissue injury. Qingwenzhike (QWZK) prescription has been demonstrated to be effective against respiratory viral infections in clinical practices, including coronavirus disease 2019 (COVID-19) infection. So far, the chemical compositions, protective effects on ALI, and possible anti-inflammatory mechanisms remain unknown.Methods: In this study, the compositions of QWZK were determined via the linear ion trap/electrostatic field orbital trap tandem high-resolution mass spectrometry (UHPLC-LTQ-Orbitrap MS). To test the protective effects of QWZK on ALI, an ALI model induced by lipopolysaccharide (LPS) in rats was used. The effects of QWZK on the LPS-induced ALI were evaluated by pathological changes and the number and classification of white blood cell (WBC) in bronchoalveolar lavage fluid (BALF). To investigate the possible underlying mechanisms, the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP-1), interleukin-1β (IL-1β), interleukin-18 (IL-18), and immunoregulatory-related factors interferon-γ (IFN-γ) were detected by ELISA. Furthermore, the expression of Toll-like receptor 4 (TLR4), p-IKKα/β, IKKα, IKKβ, p-IκBα, IκBα, p-NF-κB, nuclear factor-κB (NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, pro-caspase-1, apoptosis-associated speck-like protein containing CARD (ASC), and β-actin were tested by Western blot.Results: A total of 99 compounds were identified in QWZK, including 33 flavonoids, 23 phenolic acids, 3 alkaloids, 3 coumarins, 20 triterpenoids, 5 anthraquinones, and 12 others. ALI rats induced by LPS exhibited significant increase in neutrophile, significant decrease in lymphocyte, and evidently thicker alveolar wall than control animals. QWZK reversed the changes in WBC count and alveolar wall to normal level on the model of ALI induced by LPS. ELISA results revealed that QWZK significantly reduced the overexpression of proinflammatory factors IL-6, TNF-α, MCP-1, IL-1β, IL-18, and IFN-γ induced by LPS. Western blot results demonstrated that QWZK significantly downregulated the overexpression of TLR4, p-IKKα/β, p-IκBα, p-NF-κB, NLRP3, cleaved caspase-1, and ASC induced by LPS, which suggested that QWZK inhibited TLR4/NF-κB signaling pathway and NLRP3 inflammasomes.Conclusions: The chemical compositions of QWZK were first identified. It was demonstrated that QWZK showed protective effects on ALI induced by LPS. The possible underlying mechanisms of QWZK on ALI induced by LPS was via inhibiting TLR4/NF-kB signaling pathway and NLRP3 inflammasome activation. This work suggested that QWZK is a potential therapeutic candidate for the treatments of ALI and pulmonary inflammation.

scholarly journals A Study on the Effect of Traditional Chinese medicine Chaihu-guizhi Decoction Reducing the Susceptibility and Severity of Influenza in Depressed Mice

2021 ◽  
Author(s):  
Sun Qi Hui ◽  
Jingye Zhao ◽  
Jinghua Yang ◽  
Xiaochen Zhang ◽  
Qingge Zheng ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Influenza A ◽  
H1n1 Virus ◽  
Th2 Cytokines ◽  
Mice Model ◽  
Depressed Patients ◽  
Guizhi Decoction ◽  
Tnf Α ◽  
Influenza A H1n1 ◽  
Ifn Γ

Abstract Background: Depression is one of the most common illnesses in the world. In the flu season, depressed patients are more prone to influenza infection. It causes serious health problem worldwide. Chaihu-guizhi decoction (CGD) is a classic prescription to treat depressed patients with fever in clinical practice in China. However, the pharmacological activity and mechanisms of CGD against this disease have never been reported before. We investigated the changes of depressed condition, antiviral effects, anti-inflammatory, genes and protein expressions of T-helper cell type 1/type 2 (Th1/Th2) cytokines with CGD in combined mice model. This work will provide reliable evidence of the experiments for its better clinical practice. Methods: Depressed mice were dealt with by intraperitoneal injection of reserpine solution, then intranasal infection influenza A (H1N1) virus to create combined mice model. Oral administration of CGD was conducted in mice with 30.55-61.1 g/kg/d lasting up to 6 days. Physiological indicators, behavior changes, histopathological manifestations, digestive abilities, dopamine levels and virus expressions^ of the mice were detected. Moreover, levels of Th1/Th2 cytokines, including IL-2, IL-6, IL-10, IFN-γ and TNF-α, were detected in the sera of mice. Results: The extraction of CGD at dosages of 30.55-61.1 g/kg could effectively relieve the state of depression, decrease influenza virus genes expression, reduce viscera index of the lung, ameliorate lung edema and inflammation. Administration of CGD significantly down-regulated the expression of IL-6, TNF-α and IFN-γ. CGD also manifested a decreasing trend in the ratio of IFN-γ/IL-10, compared with that of model treatment groups. Conclusion: The results reveal that the CGD could treat depression syndrome in mice combined with influenza A (H1N1) virus infection by reducing inflammation and ameliorating depressive status.

scholarly journals Pudilan xiaoyan oral liquid (PDL) inhibit the replication of influenza A virus through regulating TLR3/MyD88 signaling pathway

2022 ◽  
Author(s):  
Zheng Zhihui ◽  
Yuqian Zhang ◽  
Gang Tian ◽  
Zehua Wang ◽  
Ronghua Wang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Tnf Α ◽  
Oral Liquid ◽  
Ifn Γ

Abstract Background Pudilan Xiaoyan Oral Liquid (PDL) as a famous Chinese patent medicine has been widely used for treating upper respiratory tract infection. However, the antiviral effect of PDL remain unclear. Here, the antiviral effect of in vitro and in vivo of PDL against influenza A virus were for the first time investigated. Methods The in vitro inhibitory effect of PDL on influenza A virus was investigated using MDCK cell model. The in vivo inhibitory effect on influenza virus pneumonia was evaluated with the ICR female mice (14-16 g) model infected by influenza A virus (A/FM/1/47, H1N1, mouse-adapted). Moreover, expression levels of inflammatory cytokines including TNF-α, IP10, IL-10, IL-1β, IL-6 and IFN-γ in lung tissue were measured by qRT-PCR. The potential mechanism of PDL against acute lung injury caused by influenza A virus was investigated by RT-PCR and Western blot. Results Our results indicated that in vitro PDL has a broad-spectrum inhibitory effect on different subtypes of influenza A viruses and in vivo PDL could dose-dependently prevent weight loss of mice, increase food intake and reduce mortality caused by influenza A H1N1 virus. Furthermore, PDL could markedly improve the acute lung injury caused by influenza A virus and significantly reduce the mRNA levels of inflammatory factors such as TNF-α, IP10, IL-10, IL-1β, IL-6, and IFN-γ. Mechanistic research indicated that the protective effect of PDL on viral pneumonia might be achieved by inhibiting TLR3/MyD88/IRAK4/TRAF3 signaling pathway. Conclusion PDL not only showed a good inhibitory effect on influenza A virus in vitro, but also exhibited a significant protective effect against lethal influenza virus infection in vivo. These findings provide evidence for the clinical treatment of influenza A virus infection with PDL.

scholarly journals Inflammation-induced inhibition of chaperone-mediated autophagy maintains the immunosuppressive function of murine mesenchymal stromal cells

2020 ◽  
Author(s):  
Jie Zhang ◽  
Jiefang Huang ◽  
Yuting Gu ◽  
Mingxing Xue ◽  
Fengtao Qian ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Inflammatory Cells ◽  
T Cell Proliferation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Chaperone Mediated Autophagy

AbstractMacroautophagy has been implicated in modulating the therapeutic function of mesenchymal stromal cells (MSCs). However, the biological function of chaperone-mediated autophagy (CMA) in MSCs remains elusive. Here, we found that CMA was inhibited in MSCs in response to the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). In addition, suppression of CMA by knocking down the CMA-related lysosomal receptor lysosomal-associated membrane protein 2 (LAMP-2A) in MSCs significantly enhanced the immunosuppressive effect of MSCs on T cell proliferation, and as expected, LAMP-2A overexpression in MSCs exerted the opposite effect on T cell proliferation. This effect of CMA on the immunosuppressive function of MSCs was attributed to its negative regulation of the expression of chemokine C-X-C motif ligand 10 (CXCL10), which recruits inflammatory cells, especially T cells, to MSCs, and inducible nitric oxide synthase (iNOS), which leads to the subsequent inhibition of T cell proliferation via nitric oxide (NO). Mechanistically, CMA inhibition dramatically promoted IFN-γ plus TNF-α-induced activation of NF-κB and STAT1, leading to the enhanced expression of CXCL10 and iNOS in MSCs. Furthermore, we found that IFN-γ plus TNF-α-induced AKT activation contributed to CMA inhibition in MSCs. More interestingly, CMA-deficient MSCs exhibited improved therapeutic efficacy in inflammatory liver injury. Taken together, our findings established CMA inhibition as a critical contributor to the immunosuppressive function of MSCs induced by inflammatory cytokines and highlighted a previously unknown function of CMA.

scholarly journals Anti-Inflammatory Effects of Sosiho-Tang, a Traditional Herbal Formula, on Acute Lung Injury in LPS-Sensitized Mice and -Raw 264.7 Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
La Yoon Choi ◽  
Mi Hye Kim ◽  
Da-Hwa Jung ◽  
Woong Mo Yang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Proinflammatory Cytokines ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Alveolar Wall ◽  
Herbal Formula ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory

Acute lung injury (ALI) is a series of syndromes with persistent inflammation and abnormally increased vascular permeability. Sosiho-tang (SSHT), a traditional herbal formula consisting of a mixture of seven herbs, has been used to treat allergic reactions and chronic hepatitis disease in East Asia. In this study, we determined whether SSHT has an inhibitory effect against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. 0.05, 0.55, and 5.55 mg/kg of SSHT were orally administered to C57BL/6J mice for 7 days prior to the administration of LPS. After 2 h of LPS sensitization, lung tissues were collected to confirm the lung histology and ALI-related inflammatory factors. SSHT ameliorated the LPS-induced alveolar hemorrhage, alveolar wall thickening, and the shrinkage of the alveolar spaces in the ALI mice model. Proinflammatory cytokines including IL-6, TNF-α, and IFN-γ in the lung tissue were significantly regulated in the SSHT-treated groups compared to the LPS only-treated group. Also, increases of IL-6 and TNF-α and decrease of IFN-γ expressions were dose-dependently modulated by SSHT treatment in LPS-induced raw 264.7 cells. Additionally, the translocation of NF-κB into nucleus and phosphorylation of mitogen-activated protein (MAP) kinase were significantly attenuated by the treatment of SSHT in LPS-sensitized ALI mice. SSHT showed anti-inflammatory activities by inhibiting proinflammatory cytokines and NF-κB signaling in LPS-induced ALI. This study demonstrates that SSHT has preventive effects on LPS-induced ALI by regulating inflammatory responses as an alternative for treating lung diseases.

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