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1.
J Int Med Res ; 49(3): 3000605211002695, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33745336

RESUMEN

Over the past several decades, studies have demonstrated the existence of bi-directional relationships between periodontal disease and systemic conditions. Periodontitis is a polymicrobial and multifactorial disease involving both host and environmental factors. Tissue destruction is primarily associated with hyperresponsiveness of the host resulting in release of inflammatory mediators. Pro-inflammatory cytokines play a major role in bacterial stimulation and tissue destruction. In addition, these cytokines are thought to underlie the associations between periodontitis and systemic conditions. Current research suggests that increased release of cytokines from host cells, referred to as the cytokine storm, is associated with disease progression in patients with coronavirus disease 2019 (COVID-19). An intersection between periodontitis and pulmonary disease is biologically plausible. Hence, we reviewed the evidence linking COVID-19, cytokines, and periodontal disease. Plaque control is essential to prevent exchange of bacteria between the mouth and the lungs, reducing the risk of lung disease. Understanding these associations may help identify individuals at high risk and deliver appropriate care at early stages.


Asunto(s)
/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Placa Dental/inmunología , Interacciones Huésped-Patógeno/inmunología , Periodontitis/inmunología , Estrés Psicológico/inmunología , /complicaciones , /virología , Síndrome de Liberación de Citoquinas/complicaciones , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/virología , Placa Dental/complicaciones , Placa Dental/genética , Placa Dental/virología , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Humanos , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Pulmón/inmunología , Pulmón/patología , Pulmón/virología , Patrón Molecular Asociado a Patógenos/inmunología , Patrón Molecular Asociado a Patógenos/metabolismo , Periodontitis/complicaciones , Periodontitis/genética , Periodontitis/virología , Transducción de Señal , Estrés Psicológico/complicaciones , Estrés Psicológico/genética , Estrés Psicológico/virología , Diente/inmunología , Diente/patología , Diente/virología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
2.
Zhongguo Zhong Yao Za Zhi ; 46(2): 436-443, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33645133

RESUMEN

The aim of this paper was to observe the effect of Xinfeng Capsules(XFC)-containing serum on the apoptosis and inflammation of fibroblast-like synoviocytes(FLS) in rheumatoid arthritis(RA) induced by tumor necrosis factor-α(TNF-α), so as to investigate the mechanism of XFC in the treatment of RA. RA-FLS immortalized cell line was established, and XFC drug-containing serum was prepared. CCK-8, ELISA, RT-qPCR, immunofluorescence and TUNEL were used to observe the effect of XFC-containing serum on RA-FLS apoptosis and inflammatory indexes. CCK-8 results showed that the optimal concentration and time of TNF-α on RA-FLS were 10 ng·mL~(-1) and 48 h, respectively; and the optimal concentration and time of XFC on RA-FLS were 6.48 mg·g~(-1) and 72 h, respectively. The results of ELISA showed that compared with RA-FLS group, the expressions of TNF-α, IL-1ß, IL-6, IL-8 in TNF-α+RA-FLS group were significantly increased, while the expressions of IL-4 and IL-10 were significantly decreased(P<0.01); after intervention with XFC-containing serum, the expressions of TNF-α, IL-1ß, IL-6, IL-8 were significantly decreased, whereas the expressions of IL-4 and IL-10 were significantly increased(P<0.01). The results of RT-qPCR showed that compared with RA-FLS group, the mRNA expressions of Fas, FasL, caspase-3, caspase-8, Bax, Bcl-X1 in TNF-α+RA-FLS group were significantly decreased, while the mRNA expression of Bcl-2 was significantly increased(P<0.001); after intervention with XFC-containing serum, the mRNA expressions of Fas, FasL, caspase-3, caspase-8, Bax, Bcl-X1 were significantly increased, whereas the mRNA expression of Bcl-2 was significantly decreased(P<0.01). The results of immunofluorescence showed that compared with RA-FLS group, the protein expressions of caspase-3 and Bax in TNF-α+RA-FLS group was significantly lower than those in RA-FLS group(P<0.05); after intervention with XFC-containing serum, the protein expressions of caspase-3 and Bax were significantly increased, whereas the protein expression of Bcl-2 was significantly decreased(P<0.05). TUNEL results showed that compared with RA-FLS group, the apoptosis of TNF-α+RA-FLS group was decreased(P<0.05); after intervention with XFC-containing serum, the apoptosis was significantly increased(P<0.05). One of the mechanisms of XFC in the treatment of RA is to promote the apoptosis of RA-FLS and inhibit its inflammatory reaction.


Asunto(s)
Artritis Reumatoide , Sinoviocitos , Apoptosis , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Cápsulas , Células Cultivadas , Medicamentos Herbarios Chinos , Fibroblastos , Humanos , Inflamación , Membrana Sinovial , Factor de Necrosis Tumoral alfa/genética
3.
Arch Immunol Ther Exp (Warsz) ; 69(1): 6, 2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33683459

RESUMEN

The pathophysiology of rotator cuff tendinopathy is not fully understood, particularly in terms of the local inflammatory process. This study aimed to investigate the expression of selected molecules in the tumour necrosis factor (TNF)-α transduction pathway, including TNF-α, TNF receptor 1 (TNFR1), neutral sphingomyelinase activation associated factor (NSMAF), caspase 3 (Casp3), and interleukin (IL)-8, in patients with rotator cuff tendinopathy that had undergone surgical treatment. We included 44 participants that underwent arthroscopy, due to rotator cuff tendinopathy. Samples from the injured tendon were collected during arthroscopy, and RT-PCR was performed to determine gene expression. Pearson correlation analyses or U-Mann-Whitney test were performed to identify associations with the following parameters: sex, age at admission, body mass index, the presence of night pain, previous treatment (nonsteroidal anti-inflammatory drugs and/or steroids), medical history of the shoulder injury, upper subluxation of the humeral head, and the number of tendons injured. RT-PCR showed that the selected pro-inflammatory factors involved in the TNF-α signalling pathway expression levels were expressed in the tendon tissues. However, the levels of expression varied from patient to patient. Variations were over 250-fold for TNF-α, about 130-fold for TNFR1, NSMAF, and Casp3, and 1000-fold for IL-8. We could not confirm that any of the clinical parameters investigated were associated with the level of gene expression in the TNF-α pathway and IL-8.


Asunto(s)
Lesiones del Manguito de los Rotadores/inmunología , Tendones/inmunología , Factor de Necrosis Tumoral alfa/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Caspasa 3/genética , Femenino , Humanos , Interleucina-8/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Lesiones del Manguito de los Rotadores/cirugía , Transducción de Señal/fisiología , Factor de Necrosis Tumoral alfa/genética
4.
Adv Exp Med Biol ; 1275: 1-33, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33539010

RESUMEN

Protein kinases are intracellular signaling enzymes that catalyze the phosphorylation of specific residues in their target substrate proteins. They play important role for regulation of life and death decisions. The complexity of the relationship between death receptors and protein kinases' cell death decision-making mechanisms create many difficulties in the treatment of various diseases. The most of fifteen different cell death pathways, which are reported by Nomenclature Committee on Cell Death (NCCD) are protein kinase signal transduction-mediated negative or positive selections. Tumor necrosis factor (TNF) as a main player of death pathways is a dual-functioning molecule in that it can promote both cell survival or cell death. All apoptotic and necrotic signal transductions are conveyed through death domain-containing death receptors, which are expressed on the surface of nearly all human cells. In humans, eight members of the death receptor family have been identified. While the interaction of TNF with TNF Receptor 1 (TNFR1) activates various signal transduction pathways, different death receptors activate three main signal transduction pathways: nuclear factor kappa B (NF-ĸB)-mediated differentiation or pro-inflammatory cytokine synthesis, mitogen-activated protein kinase (MAPK)-mediated stress response and caspase-mediated apoptosis. The link between the NF-ĸB and the c-Jun NH2-terminal kinase (JNK) pathways comprise another check-point to regulate cell death. TNF-α also promotes the "receptor-interacting serine/threonine protein kinase 1" (RIPK1)/RIPK3/ mixed lineage kinase domain-like pseudokinase (MLKL)-dependent necrosis. Thus, necrosome is mainly comprised of MLKL, RIPK3 and, in some cases, RIPK1. In fact, RIPK1 is at the crossroad between life and death, downstream of various receptors as a regulator of endoplasmic reticulum stress-induced death. TNFR1 signaling complex (TNF-RSC), which contains multiple kinase activities, promotes phosphorylation of transforming growth factor ß-activated kinase 1 (TAK1), inhibitor of nuclear transcription factor κB (IκB) kinase (IKK) α/IKKß, IκBα, and NF-κB. IKKs affect cell-survival pathways in NF-κB-independent manner. Toll-like receptor (TLR) stimulation triggers various signaling pathways dependent on myeloid differentiation factor-88 (MyD88), Interleukin-1 receptor (IL-1R)-associated kinase (IRAK1), IRAK2 and IRAK4, lead to post-translational activation of nucleotide and oligomerization domain (NLRP3). Thereby, cell fate decisions following TLR signaling is parallel with death receptor signaling. Inhibition of IKKα/IKKß or its upstream activators sensitize cells to death by inducing RIPK1-dependent apoptosis or necroptosis. During apoptosis, several kinases of the NF-κB pathway, including IKK1 and NF-κB essential modulator (NEMO), are cleaved by cellular caspases. This event can terminate the NF-κB-derived survival signals. In both canonical and non-canonical pathways, IKK is key to NF-κB activation. Whereas, the activation process of IKK, the functions of NEMO ubiquitination, IKK-related non-canonical pathway and the nuclear transportation of NEMO and functions of IKKα are still debated in cell death. In addition, cluster of differentiation 95 (CD95)-mediated non-apoptotic signaling and CD95- death-inducing signaling complex (DISC) interactions are waiting for clarification.


Asunto(s)
Quinasa I-kappa B , Proteínas Quinasas , Apoptosis , Humanos , Quinasa I-kappa B/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Fosforilación , Proteínas Quinasas/genética , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
5.
Adv Exp Med Biol ; 1278: 257-272, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33523452

RESUMEN

The puzzling biphasic or dual roles of tumor necrosis factor α (TNF) in the inflammatory and immune responses are likely to be mediated by distinct signaling pathways transduced by one of its two receptors, e.g., TNF receptor type I (TNFR1) and TNF receptor type II (TNFR2). Unlike TNFR1 that is ubiquitously expressed on almost all types of cells, the expression of TNFR2 is rather restricted to certain types of cells, such as T lymphocytes. There is now compelling evidence that TNFR2 is preferentially expressed by CD4+Foxp3+ regulatory T cells (Tregs), and TNFR2 plays a decisive role in the activation, expansion, in vivo function, and phenotypical stability of Tregs. In this chapter, the current understanding of the molecular basis and signaling pathway of TNF-TNFRs signal is introduced. Latest studies that have further supported and substantiated the pivotal role of TNF-TNFR2 interaction in Tregs biology and its molecular basis are discussed. The research progress regarding TNFR2-targeting treatment for autoimmune diseases and cancer is analyzed. Future study should focus on the further understanding of molecular mechanism underlying Treg-stimulatory effect of TNFR2 signal, as well as on the translation of research findings into therapeutic benefits of human patients with autoimmune diseases, allergy, allograft rejection, and cancer.


Asunto(s)
Enfermedades Autoinmunes , Neoplasias , Enfermedades Autoinmunes/terapia , Factores de Transcripción Forkhead/genética , Humanos , Neoplasias/terapia , Receptores Tipo II del Factor de Necrosis Tumoral/genética , Linfocitos T Reguladores , Factor de Necrosis Tumoral alfa/genética
6.
Nat Commun ; 12(1): 819, 2021 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-33547302

RESUMEN

Regulated cell death is essential in development and cellular homeostasis. Multi-protein platforms, including the Death-Inducing Signaling Complex (DISC), co-ordinate cell fate via a core FADD:Caspase-8 complex and its regulatory partners, such as the cell death inhibitor c-FLIP. Here, using electron microscopy, we visualize full-length procaspase-8 in complex with FADD. Our structural analysis now reveals how the FADD-nucleated tandem death effector domain (tDED) helical filament is required to orientate the procaspase-8 catalytic domains, enabling their activation via anti-parallel dimerization. Strikingly, recruitment of c-FLIPS into this complex inhibits Caspase-8 activity by altering tDED triple helix architecture, resulting in steric hindrance of the canonical tDED Type I binding site. This prevents both Caspase-8 catalytic domain assembly and tDED helical filament elongation. Our findings reveal how the plasticity, composition and architecture of the core FADD:Caspase-8 complex critically defines life/death decisions not only via the DISC, but across multiple key signaling platforms including TNF complex II, the ripoptosome, and RIPK1/RIPK3 necrosome.


Asunto(s)
Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/química , Caspasa 8/química , Proteína de Dominio de Muerte Asociada a Fas/química , Proteína Serina-Treonina Quinasas de Interacción con Receptores/química , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/genética , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/metabolismo , Caspasa 8/genética , Caspasa 8/metabolismo , Dominio Catalítico , Clonación Molecular , Microscopía por Crioelectrón , Proteínas Adaptadoras de Señalización del Receptor del Dominio de Muerte/química , Proteínas Adaptadoras de Señalización del Receptor del Dominio de Muerte/genética , Proteínas Adaptadoras de Señalización del Receptor del Dominio de Muerte/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteína de Dominio de Muerte Asociada a Fas/genética , Proteína de Dominio de Muerte Asociada a Fas/metabolismo , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Células HEK293 , Humanos , Modelos Moleculares , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Multimerización de Proteína , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Muerte Celular Regulada/genética , Factor de Necrosis Tumoral alfa/química , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
7.
Int J Mol Sci ; 22(3)2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33498456

RESUMEN

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund's adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Oligonucleótidos Antisentido/uso terapéutico , Factor de Necrosis Tumoral alfa/genética , Animales , Silenciador del Gen , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo
8.
Int J Mol Sci ; 22(3)2021 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-33498967

RESUMEN

The intestines are recognized as the main source of chronic inflammation in chronic kidney disease (CKD) and, among other cells, macrophages are involved in modulating this process as well as in the impaired immune response which also occurs in CKD patients. In this study, we evaluated the effect of Indoxyl Sulfate (IS), a protein bound uremic toxin poorly eliminated by hemodialysis, on inflammatory, oxidative stress and pro-apoptotic parameters, at the intestinal level in mice, on intestinal epithelial cells (IEC-6) and on primary murine peritoneal macrophages. C57BL/6J mice were treated with IS (800 mg/kg i.p.) for 3 or 6 h and histopathological analysis showed that IS induced intestinal inflammation and increased cyclooxygenase-2 (COX-2), nitrotyrosine and Bax expression in intestinal tissue. In IEC-6 cells, IS (125-1000 µM) increased tumor necrosis factor-α levels, COX-2 and inducible nitric oxide synthase expression and nitrotyrosine formation. Moreover, IS increased pro-oxidant, pro-inflammatory and pro-apoptotic parameters in peritoneal macrophages from IS-treated mice. Also, the serum concentration of IS and pro-inflammatory levels of cytokines resulted increased in IS-treated mice. Our results indicate that IS significantly contributes to affect intestinal homeostasis, immune response, and to induce a systemic pro-inflammatory state thus highlighting its potential role as therapeutic target in CKD patients.


Asunto(s)
Indicán/farmacología , Inflamación/inducido químicamente , Mucosa Intestinal/efectos de los fármacos , Estrés Oxidativo , Animales , Ciclooxigenasa 2/genética , Regulación de la Expresión Génica , Indicán/toxicidad , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Mucosa Intestinal/fisiopatología , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/genética , Insuficiencia Renal Crónica , Factor de Necrosis Tumoral alfa/genética , Tirosina/análogos & derivados , Tirosina/genética , Proteína X Asociada a bcl-2/genética
9.
Carbohydr Polym ; 256: 117514, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33483035

RESUMEN

The physicochemical properties, structural features and structure-immunomodulatory activity relationship of pectic polysaccharides from the white asparagus (Asparagus officinalis L.) skin were systematically studied. Using sequential ethanol precipitation, five sub-fractions namely WASP-40, WASP-50, WASP-60, WASP-70 and WASP-80 with distinct degree of esterification (DE) and molecular weight (Mw) were obtained. The Mw and DE values were decreased with the increase of the ethanol concentrations. Structurally, although 4-α-D-GalpA was the dominant sugar residue in all fractions, the molar ratios were decreased, whereas other sugar residues including arabinose- and mannose-based sugar residues overall increased with the increase of ethanol concentration. In addition, the effects of sub-fractions on the RAW 264.7 cells indicated that pectic polysaccharides with the higher DE value showed a stronger immunomodulatory activity. Moreover, the structure-activity relationship was also discussed in this study, which extends the value-added application of asparagus and its processing by-products.


Asunto(s)
Asparagus (Planta)/química , Expresión Génica/efectos de los fármacos , Factores Inmunológicos/química , Fagocitosis/efectos de los fármacos , Polisacáridos/química , Animales , Arabinosa/aislamiento & purificación , Secuencia de Carbohidratos , Proliferación Celular/efectos de los fármacos , Fraccionamiento Químico/métodos , Ésteres/química , Factores Inmunológicos/aislamiento & purificación , Factores Inmunológicos/farmacología , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Manosa/aislamiento & purificación , Ratones , Peso Molecular , Extractos Vegetales/química , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Células RAW 264.7 , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
10.
Carbohydr Polym ; 255: 117392, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33436221

RESUMEN

Fructooligosaccharide was isolated from Polygonatum Cyrtonema Hua (PFOS) for the first time. Structure characterized using FT-IR, MALDI-TOF-MS, NMR, AFM, and TEM, indicated that PFOS was graminan-type fructan with a degree of polymerization ranging from 5 to 10. A murine model of lipopolysaccharide (LPS)-induced peritonitis was used to evaluate the in vivo anti-inflammatory and lung protective efficacy of PFOS. The result shown that pretreatment with PFOS (1.0 mg/mL) in peritonitis-induced mice could significantly inhibit the level of pro-inflammatory cytokines (TNF-α, IL-1ß) in serum (P < 0.001), increase mice survival rate from 12.5 % to 54 % (P < 0.05), and alleviated lung injury through ameliorating the damage of the pulmonary cellular architecture and reducing inflammatory monocyte accumulation in lung tissue. This effect of oligosaccharides could explain the traditional usage of P. cyrtonema as a tonic medicine for respiratory problems and it could be used as a potential natural ingredient with anti-inflammatory activity.


Asunto(s)
Lesión Pulmonar Aguda/prevención & control , Antiinflamatorios/farmacología , Pulmón/efectos de los fármacos , Oligosacáridos/farmacología , Peritonitis/tratamiento farmacológico , Polygonatum/química , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/mortalidad , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Movimiento Celular/efectos de los fármacos , Movimiento Celular/inmunología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Expresión Génica , Humanos , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Lipopolisacáridos/administración & dosificación , Pulmón/inmunología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Monocitos/efectos de los fármacos , Monocitos/inmunología , Monocitos/patología , Oligosacáridos/química , Oligosacáridos/aislamiento & purificación , Peritonitis/inducido químicamente , Peritonitis/inmunología , Peritonitis/mortalidad , Análisis de Supervivencia , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
11.
Int J Mol Sci ; 22(3)2021 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-33513808

RESUMEN

There is little known about the effect of the periodontopathogen Filifactor alocis on macrophages as key cells of the innate immune defense in the periodontium. Therefore, the aim of the present study was to investigate the effect of F. alocis and additionally of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) on visfatin and other pro-inflammatory and proteolytic molecules associated with periodontitis in human macrophages. The presence of macrophage markers CD14, CD86, CD68, and CD163 was examined in gingival biopsies from healthy individuals and periodontitis patients. Human macrophages were incubated with F. alocis and TNFα for up to 2 d. The effects of both stimulants on macrophages were determined by real-time PCR, ELISA, immunocytochemistry, and immunofluorescence. F. alocis was able to significantly stimulate the synthesis of visfatin by human macrophages using TLR2 and MAPK pathways. In addition to visfatin, F. alocis was also able to increase the synthesis of cyclooxygenase 2, TNFα, and matrix metalloproteinase 1. Like F. alocis, TNFα was also able to stimulate the production of these proinflammatory and proteolytic molecules. Our results highlight the pathogenetic role of F. alocis in periodontal diseases and also underline the involvement of visfatin in the aetiopathogenesis of periodontitis.


Asunto(s)
Clostridiales/inmunología , Encía/metabolismo , Macrófagos/metabolismo , Nicotinamida Fosforribosiltransferasa/biosíntesis , Periodontitis/inmunología , Receptor Toll-Like 2/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/genética , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígeno B7-2/genética , Antígeno B7-2/metabolismo , Ciclooxigenasa 2/biosíntesis , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Encía/citología , Encía/patología , Humanos , Inmunohistoquímica , Receptores de Lipopolisacáridos/genética , Receptores de Lipopolisacáridos/metabolismo , Sistema de Señalización de MAP Quinasas/inmunología , Macrófagos/efectos de los fármacos , Metaloproteinasa 1 de la Matriz/biosíntesis , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 1 de la Matriz/metabolismo , Nicotinamida Fosforribosiltransferasa/genética , Nicotinamida Fosforribosiltransferasa/metabolismo , Periodontitis/metabolismo , Periodontitis/microbiología , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
12.
Arch Virol ; 166(2): 511-519, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33394172

RESUMEN

Porcine reproductive and respiratory syndrome virus (PRRSV, species Betaarterivirus suid 1 or 2) is a major pathogen affecting pigs on farms throughout the world. miR-296-3p is a multifunctional microRNA involved in the regulation of the inflammatory response in mice and humans. However, little is known about the biological functions of miR-296-3p in pigs. In this study, we used a highly pathogenic PRRSV-2 (species Betaarterivirus suid 2) strain to show that PRRSV infection robustly downregulates the expression of miR-296-3p in porcine alveolar macrophages (PAMs). Furthermore, we demonstrated that overexpression of miR-296-3p increases the replication of highly pathogenic (HP)-PRRSV in PAMs. Notably, the overexpression of miR-296-3p inhibited the induction of TNF-α, even with increased viral replication, compared with that in the HP-PRRSV-infected control group. We also demonstrated that miR-296-3p targets IRF1-facilitated viral infection and modulates the expression of TNF-α in PAMs during HP-PRRSV infection and that IRF1 regulates the expression of TNF-α by activating the TNF promoter via IRF1 response elements. In summary, these findings show that HP-PRRSV infection activates the IRF1/TNF-α signaling axis in PAMs by downregulating host miR-296-3p. This extends our understanding of the inflammatory response induced by HP-PRRSV infection.


Asunto(s)
Regulación hacia Abajo/genética , Factor 1 Regulador del Interferón/genética , Macrófagos Alveolares/virología , MicroARNs/genética , Síndrome Respiratorio y de la Reproducción Porcina/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Porcinos/virología , Factor de Necrosis Tumoral alfa/genética , Animales , Línea Celular , Chlorocebus aethiops , Perfilación de la Expresión Génica/métodos , Células HEK293 , Interacciones Huésped-Patógeno/genética , Humanos , Síndrome Respiratorio y de la Reproducción Porcina/virología , Transducción de Señal/genética , Porcinos/genética , Transcriptoma/genética , Replicación Viral/genética
13.
Exp Parasitol ; 222: 108063, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33412170

RESUMEN

Leishmaniasis is one of the most neglected tropical infectious diseases in the world. The emergence of drug resistance and toxicity and the high cost of the available drugs with a lack of new anti-leishmanial drugs highlight the need to search for newer therapies with anti-leishmanial activities. Due to the mesenchymal stem cell (MSC) immunomodulatory capacity, they have been applied in a wide variety of disorders. In this study, the potential effects of adipose-derived MSC (AD-MSCs) therapy and its combination with glucantime were evaluated in a murine model of cutaneous leishmaniasis induced by L. major. The results showed that AD-MSCs improved wound healing and decreased parasite burden. The real-time PCR results obtained from mice treated with AD-MSCs showed that IL-12 and TNF-α genes were upregulated. IL-10, arginase, and FOXP3 genes were downregulated whereas no differences in expression of the IL-4 gene were found. Overall, it seems that AD-MSCs therapy enhances Th1 immune response in L. major infected BALB/c mice. Unexpectedly, our results showed that the association of glucantime to AD-MSCs treatments did not lead to an increment in the anti-leishmanial activity.


Asunto(s)
Leishmania major , Leishmaniasis Cutánea/terapia , Células Madre Mesenquimatosas/inmunología , Análisis de Varianza , Animales , Arginasa/genética , Arginasa/metabolismo , Regulación hacia Abajo , Femenino , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Expresión Génica , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-12/genética , Interleucina-12/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Ratones , Ratones Endogámicos BALB C , Células TH1/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba
14.
J Sci Food Agric ; 101(3): 863-870, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33433910

RESUMEN

BACKGROUND: Protecting the intestinal mucosa from being destroyed helps reduce the inflammation caused by acute pancreatitis (AP). In this study, whether okra pectin (OP) could attenuate the inflammation of AP through protecting the intestinal barrier was investigated. RESULTS: OP was obtained from crude okra pectin (COP) through the purification by DEAE cellulose 52 column. Supplementation with OP or COP in advance reduced the severity of AP, as revealed by lower serum amylase and lipase levels, abated pancreatic edema, attenuated myeloperoxidase activity and pancreas histology. OP or COP inhibited the production of pancreatic proinflammatory cytokines, including tumor necrosis factor-α and interleukin-6. In addition, the upregulation of AP-related proteins including ZO-1, occludin, the antibacterial peptide-defensin-1 (DEFB1) and cathelicidin-related antimicrobial peptide (CRAMP), as well as the histological examination of colon injuries, demonstrated that OP or COP provision could effectively maintain intestinal barrier function. Ultimately, dietary OP or COP supplementation could inhibit AP-induced intestinal inflammation. For the above, the effect of OP was better than COP. CONCLUSION: Dietary OP supplementation could be considered as a preventive method that effectively interferes with intestinal damage and attenuates inflammatory responses trigged by AP. © 2020 Society of Chemical Industry.


Asunto(s)
Abelmoschus/química , Ceruletida/efectos adversos , Mucosa Intestinal/efectos de los fármacos , Pancreatitis/tratamiento farmacológico , Pectinas/administración & dosificación , Extractos Vegetales/administración & dosificación , Animales , Citocinas/genética , Citocinas/inmunología , Frutas/química , Humanos , Mucosa Intestinal/inmunología , Masculino , Ratones , Ocludina/genética , Ocludina/inmunología , Pancreatitis/inducido químicamente , Pancreatitis/genética , Pancreatitis/inmunología , Pectinas/química , Extractos Vegetales/química , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Proteína de la Zonula Occludens-1/genética , Proteína de la Zonula Occludens-1/inmunología
15.
Gene ; 775: 145441, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33482280

RESUMEN

Exercise training with anti-inflammatory effects can improve insulin sensitivity in muscle tissue. This study investigated the effects of eight-week swimming exercises on lipid profile, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and peroxisome proliferator-activated receptor gamma (PPAR-γ) in gastrocnemius muscle of rats fed with high-fat diet (HFD). Thirty-two healthy male Wistar rats (8 weeks, 200 ± 20 g) were randomly divided into four groups (n = 8 each group): the control (C), aerobic exercise (E), HFD, and HFD + aerobic exercise (HFD & E). The exercise training protocol consisted of swimming 60 min/day, 5 days/week for eight weeks. Serum levels of glucose, insulin, and lipid profile were measured at end of the study. Protein expressions of TLR4, TNF-α, and IL-6 were determined by immunohistochemical method. Gene expression of TLR4/MyD88, TNF-α, IL-6, and PPAR-γ was evaluated by a real-time polymerase chain reaction in gastrocnemius muscle. HFD fed rats showed higher levels of cholesterol and LDL-c that were similar in weight gain. Meanwhile, the HFD group had a higher gene expression of TLR4, MyD88, TNF-α, IL-6, and lower gene expression of PPAR-γ compared to the control group (p < 0.05). Muscle protein expression of TLR4, TNF-α, IL-6 was lower in the E and HFD&E groups (especially when compared to HFD group, P < 0.05). We also showed a decrease in TLR4/MyD88 mRNA and an increase in PPAR-γ mRNA in gastrocnemius of E and HFD&E groups (compared to HFD group, p < 0.05). Insulin resistance in HFD&E groups show a significant decrease compared to the HFD group (p < 0.05). It seems that swimming aerobic exercise for eight weeks controlled the destructive effects of HFD on muscle inflammatory pathways along with the down-regulation of the TLR4/MyD88, inflammatory cytokine, and up-regulation PPAR-γ mRNA. It appears that the down-regulation in the expression of TLR4/MyD88 mRNA reduces the muscle pro-inflammatory cytokines, such as IL-6 and TNF-α, whose action may be caused by the adaptation of swimming aerobic exercise (an increase of PPAR-γ). Therefore, local and systemic inflammatory changes due to HFD and obesity may be affected by metabolic adaptations of aerobic exercise training, which requires further studies.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Resistencia a la Insulina/inmunología , Músculo Esquelético/metabolismo , Condicionamiento Físico Animal/métodos , Natación/fisiología , Animales , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Músculo Esquelético/efectos de los fármacos , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
16.
Nat Commun ; 12(1): 567, 2021 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-33495464

RESUMEN

The regulatory elements controlling gene expression during acute inflammation are not fully elucidated. Here we report the identification of a set of NF-κB-bound elements and common chromatin landscapes underlying the acute inflammatory response across cell-types and mammalian species. Using primary vascular endothelial cells (human/mouse/bovine) treated with the pro-inflammatory cytokine, Tumor Necrosis Factor-α, we identify extensive (~30%) conserved orthologous binding of NF-κB to accessible, as well as nucleosome-occluded chromatin. Regions with the highest NF-κB occupancy pre-stimulation show dramatic increases in NF-κB binding and chromatin accessibility post-stimulation. These 'pre-bound' regions are typically conserved (~56%), contain multiple NF-κB motifs, are utilized by diverse cell types, and overlap rare non-coding mutations and common genetic variation associated with both inflammatory and cardiovascular phenotypes. Genetic ablation of conserved, 'pre-bound' NF-κB regions within the super-enhancer associated with the chemokine-encoding CCL2 gene and elsewhere supports the functional relevance of these elements.


Asunto(s)
Cromatina/genética , Células Endoteliales/metabolismo , Regulación de la Expresión Génica/genética , Inflamación/genética , FN-kappa B/metabolismo , Secuencias Reguladoras de Ácidos Nucleicos/genética , Enfermedad Aguda , Animales , Sitios de Unión/genética , Bovinos , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Cromatina/metabolismo , Secuencia Conservada/genética , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/metabolismo , Inflamación/patología , Lógica , Ratones , Modelos Genéticos , Unión Proteica , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/farmacología
17.
Arch Virol ; 166(4): 1035-1045, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33438105

RESUMEN

Human endogenous retrovirus W family envelope protein (HERV-W env) is associated with several neurological and psychiatric disorders, including multiple sclerosis (MS) and schizophrenia. Clinical studies have demonstrated a common link between inflammatory abnormalities and HERV-W env in neuropsychiatric diseases. Nonetheless, the molecular mechanisms by which HERV-W env mediates neuroinflammation are still unclear. In this study, we found that HERV-W env significantly increased the mRNA and protein levels of TNF-α and IL-10 in U251 and A172 cells. HERV-W env also induced a notable increase in Toll-like receptor 4 (TLR4). Knockdown of TLR4 impaired the expressions of TNF-α and IL-10 induced by HERV-W env. Overexpression of HERV-W env led to the upregulation of MyD88 but caused a decrease in MyD88s. MyD88s overexpression suppressed the expressions of TNF-α and IL-10 induced by HERV-W env. These findings indicate that HERV-W env upregulates the expressions of IL-10 and TNF-α by inhibiting the production of MyD88s in glial cells. This work sheds light on the immune pathogenesis of HERV-W env in neuropsychiatric disorders.


Asunto(s)
Retrovirus Endógenos/metabolismo , Productos del Gen env/metabolismo , Interleucina-10/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Neuroglía/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Línea Celular Tumoral , Humanos , Inflamación , Interleucina-10/genética , Factor 88 de Diferenciación Mieloide/genética , Neuroglía/inmunología , ARN Mensajero/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/genética
18.
Artículo en Inglés | MEDLINE | ID: mdl-33435295

RESUMEN

Smoking is a well-recognized risk factor for oral mucosal and periodontal diseases. Nicotine is an important component of cigarette smoke. This study aims to investigate the impact of nicotine on the viability and inflammatory mediator production of an oral epithelial cell line in the presence of various inflammatory stimuli. Oral epithelial HSC-2 cells were challenged with nicotine (10-8-10-2 M) for 24 h in the presence or absence of Porphyromonas gingivalis lipopolysaccharide (LPS, 1 µg/mL) or tumor necrosis factor (TNF)-α (10-7 M) for 24 h. The cell proliferation/viability was determined by MTT assay. Gene expression of interleukin (IL)-8, intercellular adhesion molecule (ICAM)-1, and ß-defensin was assayed by qPCR. The production of IL-8 protein and cell surface expression of ICAM-1 was assessed by ELISA and flow cytometry, respectively. Proliferation/viability of HSC-2 cells was unaffected by nicotine at concentrations up to 10-3 M and inhibited at 10-2 M. Nicotine had no significant effect on the basal expression of IL-8, ICAM-1, and ß-defensin. At the same time, it significantly diminished P. gingivalis LPS or the TNF-α-induced expression levels of these factors. Within the limitations of this study, the first evidence was provided in vitro that nicotine probably exerts a suppressive effect on the production of inflammatory mediators and antimicrobial peptides in human oral epithelial cells.


Asunto(s)
Nicotina , Porphyromonas gingivalis , Células Cultivadas , Células Epiteliales , Humanos , Mediadores de Inflamación , Lipopolisacáridos/toxicidad , Nicotina/toxicidad , Factor de Necrosis Tumoral alfa/genética
19.
Int J Nanomedicine ; 16: 133-145, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33447032

RESUMEN

Background: Rheumatoid arthritis (RA) is an autoimmune disease that underlies chronic inflammation of the synovial membrane. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat RA. However, a long list of adverse events associated with long-term treatment regimens with NSAIDs negatively influences patient compliance and therapeutic outcomes. Aim: The aim of this work was to achieve site-specific delivery of celecoxib-loaded spanlastic nano-vesicle-based delivery system to the inflamed joints, avoiding systemic administration of large doses. Methodology: To develop spanlastic nanovesicles for transdermal delivery of celecoxib, modified injection method was adopted using Tween 80 or Brij as edge activators. Entrapment efficiency, vesicle size, ex vivo permeation, and morphology of the prepared nano-vesicles were characterized. Carbopol-based gels containing the selected formulations were prepared, and their clarity, pH, rheological performance, and ex vivo permeation were characterized. Celecoxib-loaded niosomes and noisome-containing gels were developed for comparison. The in vivo efficacy of the selected formulations was evaluated in a rat model of Freund's complete adjuvant-induced arthritis. Different inflammatory markers including TNF-α, NF-кB and COX-2 were assessed in paw tissue before and after treatment. Results: The size and entrapment efficiency of the selected spanlastic nano-vesicle formulation were 112.5 ± 3.6 nm, and 83.6 ± 2.3%, respectively. This formulation has shown the highest transdermal flux and permeability coefficient compared to the other investigated formulations. The spanlastics-containing gel of celecoxib has shown transdermal flux of 6.9 ± 0.25 µg/cm2/hr while the celecoxib niosomes-containing gel and unprocessed celecoxib-loaded gel have shown 5.2 ± 0.12 µg/cm2/hr and 0.64 ± 0.09 µg/cm2/hr, respectively. In the animal model of RA, the celecoxib-loaded spanlastics-containing gel significantly reduced edema circumference and significantly suppressed TNF-α, NF-кB and COX-2 levels compared to the niosomes-containing gel, the marketed diclofenac sodium gel, and unprocessed celecoxib-loaded gel. Conclusion: The spanlastic nano-vesicle-containing gel represents a more efficient site-specific treatment for topical treatment of chronic inflammation like RA, compared to commercial and other conventional alternatives.


Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Celecoxib/uso terapéutico , Ciclooxigenasa 2/metabolismo , Regulación hacia Abajo , FN-kappa B/metabolismo , Nanopartículas/química , Factor de Necrosis Tumoral alfa/metabolismo , Administración Cutánea , Administración Tópica , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/genética , Celecoxib/farmacología , Ciclooxigenasa 2/genética , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Adyuvante de Freund , Regulación de la Expresión Génica/efectos de los fármacos , Cinética , Liposomas , Masculino , Ratones , FN-kappa B/genética , Tamaño de la Partícula , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Reología , Absorción Cutánea/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética
20.
Gene ; 767: 145079, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32860901

RESUMEN

Neuropathic pain is a most challenging diseases worldwide, caused by the injury of nerve system. CircularRNAs (circRNAs) are revealed to be involved in various diseases, includingneuropathic pain. However, the waycircRNAsparticipate in the progress ofneuropathic painstill needs further study. Identifyingthe possible circRNAexpression patterns of neuropathic painis of great significance to understand its underlying mechanism. Previously, circ_0005075 has been regarded as an important oncogene in multiple cancers and it has been characterized as an inflammation­associated circRNA in various processes. Nevertheless, the functional role of circ_0005075 in neuropathic pain development is still poorly known. In our present study, we observed circ_0005075 was obviously increased in CCI rat models. Knockdown of circ_0005075 repressed thebehaviors of neuropathic pain including mechanical and thermal hyperalgesia. Moreover, loss of circ_0005075 could repress the neuroinflammation via targeting COX-2, IL-6 and TNF-α whereas inducing IL-10 in vivo. Additionally, we predicted miR-151a-3p as the potential target of circ_0005075 using bioinformatics analysis. We displayed that miR-151a-3p was greatly reduced in CCI rats and circ_0005075 reversed the repressive effect of miR-151a-3p on neuropathic pain. For another, NOTCH2 has been shown to induce a variety of intracellular responses correlated withneuropathic pain. Here, we found NOTCH2 expression was strongly induced in CCI rats and miR-151a-3p. In addition, circ_0005075 significantly rescued NOTCH2 expression, which could be repressed by miR-151a-3p. To sum up, we indicated that loss ofcirc_0005075relieved neuropathic pain progression by inducement of miR-151a-3p and inactivation of NOTCH2 signaling.


Asunto(s)
MicroARNs/genética , Neuralgia/genética , ARN Circular/genética , Animales , Progresión de la Enfermedad , Inflamación/metabolismo , Interleucina-6/genética , Masculino , MicroARNs/metabolismo , Neuralgia/metabolismo , ARN Largo no Codificante/genética , Ratas , Ratas Sprague-Dawley , Receptor Notch2/genética , Receptor Notch2/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética
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