Effects of eccentric exercise on toll-like receptor 4 signaling pathway in peripheral blood mononuclear cells

2012 ◽  
Vol 112 (12) ◽  
pp. 2011-2018 ◽  
Author(s):  
Rodrigo Fernandez-Gonzalo ◽  
José A. De Paz ◽  
Paula Rodriguez-Miguelez ◽  
María J. Cuevas ◽  
Javier González-Gallego
Keyword(s):  
Signaling Pathway ◽  
Eccentric Exercise ◽  
Mononuclear Cells ◽  
Eccentric Training ◽  
Proinflammatory Response ◽  
Peripheral Blood Mononuclear ◽  
Tlr4 Signaling ◽  
Tnf Α ◽  
Tlr4 Signaling Pathway ◽  
Myeloid Differentiation Factor

This study aimed to investigate the response of the toll-like receptor 4 (TLR4) signaling pathway to an acute bout of eccentric exercise, and to assess whether eccentric training attenuated the effects induced by acute eccentric exercise. Twenty men (22.4 ± 0.5 yr) were divided into a control group (CG, n = 8) and a training group (TG, n = 12). Both groups performed two acute eccentric bouts on a squat machine in a 9-wk interval. During this time, TG followed a 6-wk eccentric training program (3 session/wk; 3–5 sets of 10 repetitions with loads ranging between the 40 and 50% of maximal isometric voluntary contraction). CD14, TLR4, and TNF-α mRNA levels, and CD14, TLR4, myeloid differentiation factor 88, tumor necrosis factor receptor-associated factor 6, TIR-domain-containing adapter-inducing interferon-β, phospho-IκB kinases, phospho-IκB, phospho-ERK-1/2, and TNF-α protein concentration were measured in peripheral blood mononuclear cells, before, immediately, and 2 h after each eccentric bout. The first acute eccentric bout triggered a proinflammatory response mediated by an upregulation of all of the factors measured within the TLR4 signaling pathway. Following the training period and after the second acute bout, CG showed a similar proinflammatory response than that seen after the first bout. However, the eccentric training intervention decreased significantly the protein concentration of all factors analyzed in TG compared with results obtained after the first bout. These results suggest that the TLR4-signaling pathway plays a critical role in the proinflammatory response seen after acute eccentric exercise. This response was attenuated after an eccentric training program through myeloid differentiation factor 88-dependent and -independent pathways.

scholarly journals TLR4-Mediated Blunting of Inflammatory Responses to Eccentric Exercise in Young Women

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Rodrigo Fernandez-Gonzalo ◽  
José A. De Paz ◽  
Paula Rodriguez-Miguelez ◽  
María J. Cuevas ◽  
Javier González-Gallego
Keyword(s):  
Inflammatory Response ◽  
Training Program ◽  
Signaling Pathway ◽  
Young Women ◽  
Eccentric Exercise ◽  
Inflammatory Responses ◽  
Control Group ◽  
Eccentric Training ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway

This study assessed the inflammatory response mediated by the toll-like receptor 4 (TLR4) signaling pathway after acute eccentric exercise before and after an eccentric training program in women. Twenty women performed two acute eccentric bouts using a squat machine over a ~9 week interval. The training group (TG) carried out an eccentric training program during 6 weeks, while the control group (CG) did not follow any training. Protein content of markers involved in the TLR4-mediated activation of several nuclear transcription factors, such as nuclear factorκB (NF-κB), and interferon regulatory transcription factor 3 (IRF3), was analyzed. The inflammatory response after the first acute bout was similar between TG and CG, showing an upregulation of all the markers analyzed, with the exception of IRF3. After the second bout, the upregulation of TLR4 signaling pathway was blunted in TG, but not in CG, through both the myeloid differentiation factor 88- and toll/interleukin-1 receptor domain containing adapter inducing interferon-β-dependent pathways. These results highlight the role of the TLR4 in controlling the exercise-induced inflammatory response in young women. More importantly, these data suggest eccentric training may help to prevent TLR4 activation principally through NF-κB, and perhaps IRF3, downstream signaling in this population.

scholarly journals Remote ischemic per-conditioning protects against renal ischemia–reperfusion injury via suppressing gene expression of TLR4 and TNF-α in rat model

2019 ◽  
Vol 97 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Firouzeh Gholampour ◽  
Jamshid Roozbeh ◽  
Sahar Janfeshan ◽  
Zeinab Karimi
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Antioxidant Systems ◽  
Tlr4 Signaling ◽  
Tnf Α ◽  
Renal Ischemia Reperfusion Injury ◽  
Tlr4 Signaling Pathway

The pathogenesis of renal ischemia–reperfusion injury (IRI) involves both inflammatory processes and oxidative stress in the kidney. This study determined whether remote ischemic per-conditioning (RIPerC) is mediated by toll-like receptor 4 (TLR4) signaling pathway in rats. Renal IR injury was induced by occluding renal arteries for 45 min followed by 24 h of reperfusion. RIPerC included 4 cycles of 2 min of ischemia of the left femoral artery followed by 3 min of reperfusion performed at the start of renal ischemia. Rats were divided into sham, IR, and RIPerC groups. At the end of the reperfusion period, urine, blood and tissue samples were gathered. IR created kidney dysfunction, as ascertained by a significant decrease in creatinine clearance and a significant increase in sodium fractional excretion. These changes occurred in concert with a decrease in the activities of glutathione peroxidase, catalase, and superoxide dismutase with an increment in malondialdehyde levels, mRNA expression levels of TLR4 and tumor necrosis factor α (TNF-α), and histological damage in renal tissues. RIPerC treatment diminished all these changes. This study demonstrates that RIPerC has protective effects on the kidney after renal IR, which might be related to the inhibition of the TLR4 signaling pathway and augmentation of antioxidant systems.

scholarly journals Identification of Anti-Trypanosoma cruziLead Compounds with Putative Immunomodulatory Activity

2018 ◽  
Vol 62 (4) ◽  
pp. e01834-17 ◽  
Author(s):  
Dayane Andriotti Otta ◽  
Fernanda Fortes de Araújo ◽  
Vitor Bortolo de Rezende ◽  
Elaine Maria Souza-Fagundes ◽  
Silvana Maria Elói-Santos ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Mononuclear Cells ◽  
Chronic Phase ◽  
Interleukin 10 ◽  
Immunomodulatory Activity ◽  
Proinflammatory Response ◽  
Therapeutic Success ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Tnf Α

ABSTRACTIn seeking substitutions for the current Chagas disease treatment, which has several relevant side effects, new therapeutic candidates have been extensively investigated. In this context, a balanced interaction between mediators of the host immune response seems to be a key element for therapeutic success, as a proinflammatory microenvironment modulated by interleukin-10 (IL-10) is shown to be relevant to potentiate anti-Trypanosoma cruzidrug activity. This study aimed to identify the potential immunomodulatory activities of the anti-T. cruziK777, pyronaridine (PYR), and furazolidone (FUR) compounds in peripheral blood mononuclear cells (PBMC) from noninfected (NI) subjects and chronic Chagas disease (CD) patients. Our results showed low cytotoxicity to PBMC populations, with 50% cytotoxic concentrations (CC50) of 71.0 μM (K777), 9.0 μM (PYR), and greater than 20 μM (FUR). In addition, K777 showed no impact on the exposure index (EI) of phytohemagglutinin-stimulated leukocytes (PHA), while PYR and FUR treatments induced increased EI of monocytes and T lymphocytes at late stages of apoptosis in NI subjects. Moreover, K777 induced a more prominent proinflammatory response (tumor necrosis factor alpha-positive [TNF-α+] CD8+/CD4+, gamma interferon-positive [IFN-γ+] CD4+/CD8+modulated by interleukin-10-positive [IL-10+] CD4+T/CD8+T) than did PYR (TNF-α+CD8+, IL-10+CD8+) and FUR (TNF-α+CD8+, IL-10+CD8+). Signature analysis of intracytoplasmic cytokines corroborated the proinflammatory/modulated (K777) and proinflammatory (PYR and FUR) profiles previously found. In conclusion, the lead compound K777 may induce beneficial changes in the immunological profile of patients presenting the chronic phase of Chagas disease and may contribute to a more effective therapy against the disease.

Jellyfish collagen stimulates production of TNF-α and IL-6 by J774.1 cells through activation of NF-κB and JNK via TLR4 signaling pathway

2014 ◽  
Vol 58 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Agus Budiawan Naro Putra ◽  
Kosuke Nishi ◽  
Ryusuke Shiraishi ◽  
Mikiharu Doi ◽  
Takuya Sugahara
Keyword(s):  
Signaling Pathway ◽  
Tlr4 Signaling ◽  
Tnf Α ◽  
Tlr4 Signaling Pathway

Assessment of Key Elements in the Innate Immunity System Among Patients with HIV, HCV, and Coinfections of HIV/HCV

2020 ◽  
Vol 18 (3) ◽  
pp. 194-200
Author(s):  
Maryam Moradi ◽  
Alireza Tabibzadeh ◽  
Davod Javanmard ◽  
Saied Ghorbani ◽  
Farah Bokharaei-Salim ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Mononuclear Cells ◽  
Hiv Infections ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Hiv Coinfection ◽  
Tnf Α ◽  
Immunity Genes ◽  
Healthy Control ◽  
Hcv Coinfection

Background: Coinfection of Hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has a higher risk of mortality than HCV or HIV monoinfection. HCV and HIV infections are specified by systemic inflammation, but the inflammation process in HCV/HIV coinfection is much complicated and is not well characterized. Objective: The aim of this study was to analyze the expression of TLR-3, TLR-7, IL-10, IFN-1 (IFN-α, IFN-β), and TNF-α in HIV, HCV and HIV/HCV co-infected patients. Methods: Forty-five patients including HIV group (n=15), HCV group (n=15), HIV/HCV coinfection group (n=15) and healthy control group (n=15) participated. Peripheral blood mononuclear cells (PBMCs) were obtained. PBMC-RNA, HCV and HIV RNA were extracted from all subjects and cDNA was synthesized. The viral load analyzed by reverse transcription-quantitative PCR (RT-qPCR), and the expression levels of IFN-α, IFN-β, TLR-3, TLR-7, TNF, and IL-10 mRNA were quantified in PBMCs. Results: The levels of IFN-I, IL-10, and TNF-α were overexpressed in all patients’ groups (P<0.05), TLR-7 was upregulated in all groups, but this upregulation was not statistically significant (p>0.05). TLR-3 showed a decrease in all patient groups (P<0.05). The statistical analysis demonstrated that TLR-3 has a negative correlation with HIV load, whereas other genes positively correlated with HIV load. In addition, TLR-3, TNF-α, and IFN-I were negatively correlated with HCV load, whereas TLR-7 and IL-10 s were positively correlated with HCV load. Conclusion: Our results showed a significant relationship between the expression level of innate immunity genes and inflammation in HCV, HIV, and HIV/HCV coinfected patients.

scholarly journals Immunoglobulin A1 Protease, an Exoenzyme of Pathogenic Neisseriae, Is a Potent Inducer of Proinflammatory Cytokines

1999 ◽  
Vol 190 (8) ◽  
pp. 1049-1058 ◽  
Author(s):  
Dirk R. Lorenzen ◽  
Frank Düx ◽  
Uwe Wölk ◽  
Anastasios Tsirpouchtsidis ◽  
Gaby Haas ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Mononuclear Cells ◽  
Native Form ◽  
Peripheral Blood Mononuclear ◽  
Potent Inducer ◽  
Cytokine Induction ◽  
Regulatory Cytokine ◽  
Iga1 Protease ◽  
Tnf Α ◽  
Necrosis Factor

A characteristic of human pathogenic Neisseriae is the production and secretion of an immunoglobulin (Ig)A1-specific serine protease (IgA1 protease) that cleaves preferentially human IgA1 and other target proteins. Here we show a novel function for native IgA1 protease, i.e., the induction of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 from peripheral blood mononuclear cells. The capacity of IgA1 protease to elicit such cytokine responses in monocytes was enhanced in the presence of T lymphocytes. IgA1 protease did not induce the regulatory cytokine IL-10, which was, however, found in response to lipopolysaccharide and phytohemagglutinin. The immunomodulatory effects caused by IgA1 protease require a native form of the enzyme, and denaturation abolished cytokine induction. However, the proteolytic activity is not required for the cytokine induction by IgA1 protease. Our results indicate that IgA1 protease exhibits important immunostimulatory properties and may contribute substantially to the pathogenesis of neisserial infections by inducing large amounts of TNF-α and other proinflammatory cytokines. In particular, IgA1 protease may represent a key virulence determinant of bacterial meningitis.

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