scholarly journals Inflammatory response in postmenopausal osteoporotic fracture healing

2020 ◽  
Vol 9 (7) ◽  
pp. 368-385
Author(s):  
Simon K-H. Chow ◽  
Yu-Ning Chim ◽  
Jin-Yu Wang ◽  
Ronald M-Y. Wong ◽  
Victoria M-H. Choy ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Elderly Patients ◽  
Fracture Healing ◽  
Osteoporotic Fracture ◽  
Clinical Studies ◽  
Inflammatory Responses ◽  
Osteoporotic Fractures ◽  
Inflammatory Factors ◽  
Preclinical Studies ◽  
Local Inflammatory Response

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing. Cite this article: Bone Joint Res 2020;9(7):368–385.

Comparing the effect of intestinal bacteria from rabbit, pig, and chicken on inflammatory response in cultured rabbit crypt and villus

2019 ◽  
Vol 65 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Hong Xiao Cui ◽  
Xiu Rong Xu
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Intestinal Bacteria ◽  
Inflammatory Factors ◽  
Rabbit Ileum ◽  
Necrosis Factor Alpha ◽  
Heat Treated ◽  
Tnf Α ◽  
Factor Alpha ◽  
Anti Inflammatory

Rabbit is susceptible to intestinal infection, which often results in severe inflammatory response. To investigate whether the special community structure of rabbit intestinal bacteria contributes to this susceptibility, we compared the inflammatory responses of isolated rabbit crypt and villus to heat-treated total bacteria in pig, chicken, and rabbit ileal contents. The dominant phylum in pig and chicken ileum was Firmicutes, while Bacteroidetes was dominant in rabbit ileum. The intestinal bacteria from rabbit induced higher expression of toll-like receptor 4 (TLR4) in rabbit crypt and villus (P < 0.05). TLR2 and TLR3 expression was obviously stimulated by chicken and pig intestinal bacteria (P < 0.05) but not by those of rabbit. The ileal bacteria from those three animals all increased the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in crypts and villus (P < 0.05). Chicken and pig ileal bacteria also stimulated the expression of anti-inflammatory factors interferon beta (IFN-β) and IL-10 (P < 0.05), while those of rabbit did not (P > 0.05). In conclusion, a higher abundance of Gram-negative bacteria in rabbit ileum did not lead to more expressive pro-inflammatory cytokines in isolated rabbit crypt and villus, but a higher percentage of Lactobacillus in chicken ileum might result in more expressive anti-inflammatory factors.

scholarly journals A Regulatory Role for Interleukin 4 in Differential Inflammatory Responses in the Lung following Infection of Mice Primed with Th1- or Th2-Inducing Pertussis Vaccines

2000 ◽  
Vol 68 (3) ◽  
pp. 1383-1390 ◽  
Author(s):  
Peter McGuirk ◽  
Kingston H. G. Mills
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Th2 Cells ◽  
Infection Model ◽  
Local Production ◽  
Local Inflammatory Response ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells ◽  
Th1 And Th2

ABSTRACT Protection against infectious pathogens at mucosal surfaces is dependent on local antibody responses, production of inflammatory mediators, and recruitment of immune effector cells to the site of infection. Since Th1 and Th2 cells produce cytokines with pro- and anti-inflammatory activities, immunization with vaccines that induce these T-cell subtypes may regulate the subsequent inflammatory response to infection. We have demonstrated that immunization of mice with pertussis whole-cell or acellular vaccines (Pw or Pa) selectively induces Th1 and Th2 cells, respectively. In this study we have used a murine respiratory-infection model to demonstrate that priming with a Th1- or Th2-inducing pertussis vaccine can influence the local inflammatory response and immune effector cells in the lung following aerosol challenge with Bordetella pertussis. Analysis of bronchoalveolar lavage (BAL) fluid taken during the course of B. pertussis infection of naı̈ve mice or mice immunized with Pw revealed an early influx of neutrophils and local production of interleukin 1β (IL-1β) in the lungs. In contrast, neutrophil infiltration and IL-1β production were not observed following challenge of mice immunized with the Th2-inducing Pa. Conversely, during infection local production of IL-6 and IL-1ra was significantly greater in mice immunized with Pa than in those immunized with Pw. Studies of knockout mice revealed neutrophil and lymphocyte infiltration in the lungs following B. pertussis infection of IL-4-defective (IL-4−/−) mice but not in wild-type mice immunized with Pa. Furthermore, the levels of IL-1β, IL-6, and IL-1ra in Pa-immunized IL-4−/− mice were comparable to those in mice immunized with Pw. These results demonstrate distinct influences of Th1- and Th2-inducing vaccines on the protective inflammatory responses in the lungs following challenge with B. pertussis and implicate IL-4 as an important regulator of inflammatory-cell recruitment.

scholarly journals RhTrx-1 ameliorates miroglial neuroinflammation after cerebral ischemic stroke

2020 ◽  
Author(s):  
Yang Jiao ◽  
Jianjian Wang ◽  
Huixue Zhang ◽  
Yuze Cao ◽  
Yang Qu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Inflammatory Factors ◽  
Experimental Stroke ◽  
Inflammasome Activation ◽  
Cerebral Ischemic

Abstract Background Microglia are rapidly activated after ischemic stroke and participate in the occurrence of neuroinflammation, which exacerbates the injury of ischemic stroke. Receptor Interacting Serine Threonine Kinase 1 (RIPK1) is thought to be involved in the development of inflammatory responses, but its role in ischemic microglia remains unclear. Here, we applied recombinant human thioredoxin-1 (rhTrx-1), a potential neuroprotective agent, to explore the role of rhTrx-1 in inhibiting RIPK1-mediated neuroinflammatory responses in microglia. Method Middle cerebral artery occlusion (MCAO) and Oxygen and glucose deprivation (OGD) were conducted for in vivo and in vitro experimental stroke models. The expression of RIPK1 in microglia after ischemia was examined. The inflammatory response of microglia was analyzed after treatment with rhTrx-1 and Necrostatin-1 (Nec-1, inhibitors of RIPK1), and the mechanisms were explored. In addition, the effects of rhTrx-1 on neurobehavioral deficits and cerebral infarct volume were examined. Results RIPK1 expression was detected in microglia after ischemia. Molecular docking results showed that rhTrx-1 could directly bind to RIPK1. In vitro experiments found that rhTrx-1 reduced necroptosis, mitochondrial membrane potential damage, Reactive oxygen species (ROS) accumulation and NLR Family, pyrin domain-containing 3 protein (NLRP3) inflammasome activation by inhibiting RIPK-1 expression, and regulated microglial M1/M2 phenotypic changes, thereby reducing the release of inflammatory factors. Consistently, in vivo experiments found that rhTrx-1 treatment attenuated cerebral ischemic injury by inhibiting the inflammatory response. Conclusion Our study demonstrates the role of RIPK1 in microglia-arranged neuroinflammation after cerebral ischemia. Administration of rhTrx-1 provides neuroprotection in ischemic stroke-induced microglial neuroinflammation by inhibiting RIPK1 expression.

scholarly journals Mycolactone toxin induces an inflammatory response by targeting the IL-1β pathway: Mechanistic insight into Buruli ulcer pathophysiology

2020 ◽  
Vol 16 (12) ◽  
pp. e1009107
Author(s):  
M. Foulon ◽  
M. Robbe-Saule ◽  
J. Manry ◽  
L. Esnault ◽  
Y. Boucaud ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Inflammatory Factors ◽  
Dependent Manner ◽  
Local Inflammatory Response ◽  
Mechanistic Insight ◽  
Insight Into

Mycolactone, a lipid-like toxin, is the major virulence factor of Mycobacterium ulcerans, the etiological agent of Buruli ulcer. Its involvement in lesion development has been widely described in early stages of the disease, through its cytotoxic and immunosuppressive activities, but less is known about later stages. Here, we revisit the role of mycolactone in disease outcome and provide the first demonstration of the pro-inflammatory potential of this toxin. We found that the mycolactone-containing mycobacterial extracellular vesicles produced by M. ulcerans induced the production of IL-1β, a potent pro-inflammatory cytokine, in a TLR2-dependent manner, targeting NLRP3/1 inflammasomes. We show our data to be relevant in a physiological context. The in vivo injection of these mycolactone-containing vesicles induced a strong local inflammatory response and tissue damage, which were prevented by corticosteroids. Finally, several soluble pro-inflammatory factors, including IL-1β, were detected in infected tissues from mice and Buruli ulcer patients. Our results revisit Buruli ulcer pathophysiology by providing new insight, thus paving the way for the development of new therapeutic strategies taking the pro-inflammatory potential of mycolactone into account.

scholarly journals Proinflammatory Role of Angiotensin II in the Aorta of Normotensive Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Rariane Silva de Lima ◽  
Juliane Cristina de Souza Silva ◽  
Cintia Taniguti Lima ◽  
Leandro Ezequiel de Souza ◽  
Maikon Barbosa da Silva ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Control Group ◽  
Positive Staining ◽  
Perivascular Adipose Tissue ◽  
Local Inflammatory Response ◽  
Applied Dose ◽  
And Migration

Angiotensin II plays important functions in cardiovascular system mediating actions leading to inflammatory responses such as activation of VSMC in order to produce ROS, inflammatory cytokines, chemokines, and adhesion molecules. Changes in angiotensin II production could stimulate the recruitment and activation of myeloid cells initiating local inflammatory response without effect on BP. We aimed to verify if angiotensin II induces an inflammatory response in the aorta and if it correlates with variations in BP. C57Bl/6 mice treated with saline solution (0.9%, control group) or angiotensin II (30ng/kg, Ang II group) were used. BP and HR levels were measured. Immunohistochemistry for IL1-β, TGF-β, iNOS, CD45, andα-actin was performed in the aorta. BP and HR do not change. A biphasic response was observed both for IL1-βand TGF-βexpression and also for the presence of CD45 positive cells, with an acute increase (between 30 and 60 minutes) and a second increase, between 24 and 48 hours. Positive staining for iNOS increased in the earlier period (30 minutes) in perivascular adipose tissue and in a longer period (48 hours) in tunica adventitia. Immunoblotting toα-actin showed no alterations, suggesting that the applied dose of angiotensin II does not alter the aortic VSMCs phenotype. The results suggest that angiotensin II, even at doses that do not alter BP, induces the expression of inflammatory markers and migration of inflammatory cells into the aorta of normotensive mice. Thus, angiotensin II may increase the propensity to develop a cardiovascular injury, even in normotensive individuals.

Physical exercise as a human model of limited inflammatory response

1998 ◽  
Vol 76 (5) ◽  
pp. 589-597 ◽  
Author(s):  
Pang N Shek ◽  
Roy J Shephard
Keyword(s):  
Physical Exercise ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Active Phase ◽  
Human Model ◽  
Inflammatory Factors ◽  
Trauma Patients ◽  
Inflammatory Reactions ◽  
Underlying Mechanisms

An inflammatory response represents a fundamental series of humoral and cellular reaction cascades in response to infection, tissue injury, and related insults. An excessive response is commonly seen under the pathological conditions of trauma, sepsis, and burns. It is becoming increasingly evident that most, if not all, of the distinguishing features of a classical inflammatory response are detectable in an exercising individual, namely mobilization and activation of granulocytes, lymphocytes, and monocytes; release of inflammatory factors and soluble mediators; involvement of active phase reactants; and activation of the complement and other reactive humoral cascade systems. While the manifestation of many exercise-induced immune and related changes has been reported and confirmed repeatedly, the underlying mechanisms triggering and modulating the elicited immune responses are, at best, poorly understood. Unlike the exaggerated and sometimes uncontrollable inflammatory response in septic and trauma patients resulting in morbidity and mortality, strenuous and severe exercise normally elicits an inflammatory response of a subclinical nature to facilitate the repairing process for site-specific tissue damage. Regardless of the inciting event, for example trauma, infection, or exercise, and given an appropriate triggering signal, a remarkably similar sequence of inflammatory reactions can be reproduced in the affected host. Therefore, physical exercise and training represent an acceptable and good model for the study of limited inflammatory responses in humans.Key words: trauma, infection, exercise, inflammatory response, cytokines.

In Vivo Comparison of the Inflammatory Response Induced by Different Vascular Biomaterials

Vascular ◽  
2005 ◽  
Vol 13 (4) ◽  
pp. 230-235 ◽  
Author(s):  
Steven J. Busuttil ◽  
Carla Drumm ◽  
Edward F. Plow
Keyword(s):  
Stainless Steel ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Disk Surface ◽  
The Other ◽  
Vascular Prostheses ◽  
Local Inflammatory Response ◽  
Macrophage Recruitment ◽  
Significant Difference

Biomaterial implants induce a local inflammatory response. A comparison of the inflammatory cell response was made between several biomaterials commonly used as vascular prostheses. Disks of polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), aluminum, titanium, copper, and stainless steel were surgically placed into the peritoneum of mice. Recruited macrophage and neutrophil populations were measured after recovery from the disk surface and peritoneal lavage. Following peritoneal biomaterial implants, there was no difference in total neutrophil or macrophage recruitment between mice implanted with PET, PTFE, aluminum, or titanium disks. However, there was significant attenuation of total neutrophil and macrophage recruitment to stainless steel compared with the other implants. Similarly, there was no significant difference in the percentage of leukocytes adherent to the PET, aluminum, or titanium disks. Macrophage adherence to the stainless steel disks was attenuated by 19.1%, and the number of neutrophils was attenuated by 69.1% when compared with PET implant mice. Mice implanted with copper disks universally expired. Leukocyte recruitment did not differ between PET, PTFE, aluminum, or titanium disks, suggesting that these materials stimulate similar inflammatory responses. Stainless steel disks recruited both fewer neutrophils and fewer macrophages and support lower adherence of these cells than the other biomaterials. Copper incited an overwhelming and fatal response.

scholarly journals Impact of Postprandial Lipemia and Glycemia on Inflammatory Factors in over 1000 Individuals in the US and UK: Insights from the PREDICT 1 and InterCardio Studies

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1518-1518
Author(s):  
Sarah Berry ◽  
Mohsen Mazidi ◽  
Paul Franks ◽  
Ana Valdes ◽  
Naveed Sattar ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Microbial Diversity ◽  
Dietary Intervention ◽  
Inflammatory Responses ◽  
Metabolic Responses ◽  
Inflammatory Factors ◽  
Controlled Study ◽  
Low Grade ◽  
The Us ◽  
The Impact

Abstract Objectives Postprandial glycemia (PPG) and lipemia (PPL) initiate an acute inflammatory response, which may be relevant to future CVD. We characterised the impact of PPL and PPG on inflammatory responses using traditional (IL-6) and emerging (glycoprotein acetyls; GlycA) biomarkers of inflammation in a large scale, tightly controlled study (PREDICT 1; NCT03479866) and an independent validation study (InterCardio; NCT03438084). Methods The PREDICT 1 dietary intervention study of 1102 healthy individuals from the US and UK, assessed the postprandial (0–6 h) metabolic responses to sequential mixed-nutrient meals (50 g fat and 85 g carb at 0 h; 22 g fat and 71 g carb at 4 h). Baseline microbial diversity (16S Shannon diversity) and visceral fat mass (VFM; based on DXA) were also measured. Results were validated in an independent randomised crossover trial (n = 50). For both studies, glucose, triacylglycerol (TG), IL-6 and GlycA were measured at multiple intervals. Results In PREDICT 1, GlycA and IL-6 concentrations increased significantly after meals (by 4.5 and 169%; peak 6 h, respectively) but were not correlated. Peak postprandial TG and glucose concentrations were strongly associated with GlycA (r = 0.832 and r = 0.239, respectively) but not IL-6. Machine learning with cross-validation, revealed that PPL was the strongest predictor of postprandial GlycA. There was evidence of an interaction; individuals with higher microbial diversity and lower VFM had an attenuated inflammatory response. Individuals eliciting an enhanced response (30% rise at 6 h) had higher predicted CVD risk compared to the rest of the cohort. In the InterCardio study, the postprandial inflammatory increase in GlycA was also significantly correlated with PPL and varied within the four different types of fat tested. Conclusions In the first study to investigate postprandial inflammation at scale, we observed that PPL was a stronger determinant of systemic inflammation compared with PPG. The clinically significant and variable postprandial inflammatory response, and its association with lipemia and glycemia, highlights the potential for personalized dietary strategies to lower postprandial metabolic responses to reduce low grade inflammatory related diseases. Funding Sources NIHR, Wellcome Trust, Zoe Global Ltd, BBSRC DRINC.

scholarly journals ATPase Inhibitory Factor 1 Is Critical for Regulating Sevoflurane-Induced Microglial Inflammatory Responses and Caspase-3 Activation

2021 ◽  
Vol 15 ◽  
Author(s):  
Yaru Xu ◽  
Ge Gao ◽  
Xiaoru Sun ◽  
Qidong Liu ◽  
Cheng Li
Keyword(s):  
Inflammatory Response ◽  
Caspase 3 ◽  
Inflammatory Responses ◽  
Animal Experiments ◽  
Atp Synthesis ◽  
Inhibitory Factor ◽  
Inflammatory Factors ◽  
General Anesthetics ◽  
General Anesthetic ◽  
Inhibitory Factor 1

Postoperative delirium (POD) is one of the most important complications after surgery with general anesthesia, for which the neurotoxicity of general anesthetics is a high-risk factor. However, the mechanism remains largely unknown, which also hinders the effective treatment of POD. Here, we confirmed that a clinical concentration of the general anesthetic sevoflurane increased the expression of inflammatory factors and activated the caspase-3 by upregulating ATPase inhibitory factor 1 (ATPIF1) expression in microglia. Upregulation of ATPIF1 decreased the synthesis of ATP which is an important signaling molecule secreted by microglia. Extracellular supplementation with ATP attenuated the microglial inflammatory response and caspase-3 activation caused by sevoflurane or overexpression of ATPIF1. Additionally, the microglial inflammatory response further upregulated ATPIF1 expression, resulting in a positive feedback loop. Animal experiments further indicated that intraperitoneal injection of ATP significantly alleviated sevoflurane anesthesia-induced POD-related anxiety behavior and memory damage in mice. This study reveals that ATPIF1, an important protein regulating ATP synthesis, mediates sevoflurane-induced neurotoxicity in microglia. ATP supplementation may be a potential clinical treatment to alleviate sevoflurane-induced POD.

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