Tendon healing is adversely affected by low-grade inflammation

Abstract Background Tendinopathy is common, presents with pain and activity limitation, and is associated with a high risk of recurrence of the injury. Tendinopathy usually occurs as a results of a disrupted healing response to a primary injury where cellular and molecular pathways lead to low grade chronic inflammation. Main findings There has been a renewed interest in investigating the role of Inflammation in the pathogenesis of tendinopathy, in particular during the initial phases of the condition where it may not be clinically evident. Understanding the early and late stages of tendon injury pathogenesis would help develop new and effective treatments addressed at targeting the inflammatory pathways. Conclusion This review outlines the role of low-grade Inflammation in the pathogenesis of tendinopathy, stressing the role of proinflammatory cytokines, proteolytic enzymes and growth factors, and explores how Inflammation exerts a negative influence on the process of tendon healing.

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The Role of Epicardial Adipose Tissue Lymphocytes in Low-Grade Inflammation and Coronary Artery Disease

Diabetes ◽

10.2337/db18-469-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 469-P

Author(s):

MILOS MRAZ ◽

ANNA CINKAJZLOVA ◽

ZDENA LACINOVÁ ◽

JANA KLOUCKOVA ◽

HELENA KRATOCHVILOVA ◽

...

Keyword(s):

Coronary Artery Disease ◽

Adipose Tissue ◽

Coronary Artery ◽

Epicardial Adipose Tissue ◽

Low Grade ◽

Artery Disease ◽

Low Grade Inflammation

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Adipose tissue inflammation and metabolic dysfunction: a clinical perspective

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0032 ◽

2013 ◽

Vol 15 (1) ◽

Cited By ~ 2

Author(s):

Charmaine S. Tam ◽

Leanne M. Redman

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Low Grade ◽

Metabolic Dysfunction ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Proinflammatory Mediators ◽

Low Grade Inflammation

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).

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Osteopontin Expression in Human and Murine Obesity: Extensive Local Up-Regulation in Adipose Tissue but Minimal Systemic Alterations

Endocrinology ◽

10.1210/en.2007-1312 ◽

2007 ◽

Vol 149 (3) ◽

pp. 1350-1357 ◽

Cited By ~ 94

Author(s):

Florian W. Kiefer ◽

Maximilian Zeyda ◽

Jelena Todoric ◽

Joakim Huber ◽

René Geyeregger ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Plasma Concentrations ◽

Morbidly Obese ◽

Low Grade ◽

Obese Patients ◽

Multifunctional Protein ◽

Inflammatory Processes ◽

Low Grade Inflammation

Obesity is associated with a chronic low-grade inflammation characterized by macrophage infiltration of adipose tissue (AT) that may underlie the development of insulin resistance and type 2 diabetes. Osteopontin (OPN) is a multifunctional protein involved in various inflammatory processes, cell migration, and tissue remodeling. Because these processes occur in the AT of obese patients, we studied in detail the regulation of OPN expression in human and murine obesity. The study included 20 morbidly obese patients and 20 age- and sex-matched control subjects, as well as two models (diet-induced and genetic) of murine obesity. In high-fat diet-induced and genetically obese mice, OPN expression was drastically up-regulated in AT (40 and 80-fold, respectively) but remained largely unaltered in liver (<2-fold). Moreover, OPN plasma concentrations remained unchanged in both murine models of obesity, suggesting a particular local but not systemic importance for OPN. OPN expression was strongly elevated also in the AT of obese patients compared with lean subjects in both omental and sc AT. In addition, we detected three OPN isoforms to be expressed in human AT and, strikingly, an obesity induced alteration of the OPN isoform expression pattern. Analysis of AT cellular fractions revealed that OPN is exceptionally highly expressed in AT macrophages in humans and mice. Moreover, OPN expression in AT macrophages was strongly up-regulated by obesity. In conclusion, our data point toward a specific local role of OPN in obese AT. Therefore, OPN could be a critical regulator in obesity induced AT inflammation and insulin resistance.

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Role of spleen-derived IL-10 in prevention of systemic low-grade inflammation by obesity [Review]

Endocrine Journal ◽

10.1507/endocrj.ej17-0060 ◽

2017 ◽

Vol 64 (4) ◽

pp. 375-378 ◽

Cited By ~ 12

Author(s):

Koro Gotoh ◽

Kansuke Fujiwara ◽

Manabu Anai ◽

Mitsuhiro Okamoto ◽

Takayuki Masaki ◽

...

Keyword(s):

Low Grade ◽

Low Grade Inflammation

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Role of Inflammation in the Pathogenesis of Diverticular Disease

Mediators of Inflammation ◽

10.1155/2019/8328490 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Antonio Tursi ◽

Walter Elisei

Keyword(s):

Diverticular Disease ◽

Acute Diverticulitis ◽

Human Colon ◽

Recurrent Abdominal Pain ◽

Preliminary Evidence ◽

Low Grade ◽

Symptom Persistence ◽

Uncomplicated Diverticular Disease ◽

Low Grade Inflammation

Diverticulosis of the colon is the most common condition in Western societies and it is the most common anatomic alteration of the human colon. Recurrent abdominal pain is experienced by about 20% of patients with diverticulosis, but the pathophysiologic mechanisms of its occurrence are not completely understood. In the last years, several fine papers have showed clearly the role of low-grade inflammation both in the occurrence of symptoms in people having diverticulosis, both in symptom persistence following acute diverticulitis, even if the evidence available is not so strong. We do not know yet what the trigger of this low-grade inflammation occurrence is. However, some preliminary evidence found colonic dysbiosis linked to low-grade inflammation and therefore to symptom occurrence in those patients. The aim of this paper is to summarize current evidences about the role of inflammation in symptom occurrence in symptomatic uncomplicated diverticular disease and in symptom persistence after an episode of acute diverticulitis.

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Tendon healing in presence of chronic low-level inflammation: a systematic review

British Medical Bulletin ◽

10.1093/bmb/ldz035 ◽

2019 ◽

Vol 132 (1) ◽

pp. 97-116 ◽

Cited By ~ 5

Author(s):

Emanuele Chisari ◽

Laura Rehak ◽

Wasim S Khan ◽

Nicola Maffulli

Keyword(s):

Ex Vivo ◽

Tendon Healing ◽

Tendon Injury ◽

Activity Level ◽

Cochrane Library ◽

Low Level ◽

Mesh Terms ◽

The Subject ◽

Inflammatory Molecules

Abstract Background Tendinopathy is a common musculoskeletal condition affecting subjects regardless of their activity level. Multiple inflammatory molecules found in ex vivo samples of human tendons are related to the initiation or progression of tendinopathy. Their role in tendon healing is the subject of this review. Sources of data An extensive review of current literature was conducted using PubMed, Embase and Cochrane Library using the term ‘tendon’, as well as some common terms of tendon conditions such as ‘tendon injury OR (tendon damage) OR tendonitis OR tendinopathy OR (chronic tendonitis) OR tendinosis OR (chronic tendinopathy) OR enthesitis’ AND ‘healing’ AND ‘(inflammation OR immune response)’ as either key words or MeSH terms. Areas of agreement An environment characterized by a low level of chronic inflammation, together with increased expression of inflammatory cytokines and growth factors, may influence the physiological tendon healing response after treatment. Areas of controversy Most studies on this topic exhibited limited scientific translational value because of their heterogeneity. The evidence associated with preclinical studies is limited. Growing points The role of inflammation in tendon healing is still unclear, though it seems to affect the overall outcome. A thorough understanding of the biochemical mediators of healing and their pathway of pain could be used to target tendinopathy and possibly guide its management. Areas timely for developing research We require further studies with improved designs to effectively evaluate the pathogenesis and progression of tendinopathy to identify cellular and molecular targets to improve outcomes.

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A Role of Inflammation and Immunity in Essential Hypertension—Modeled and Analyzed Using Petri Nets

International Journal of Molecular Sciences ◽

10.3390/ijms21093348 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3348

Author(s):

Dorota Formanowicz ◽

Agnieszka Rybarczyk ◽

Marcin Radom ◽

Piotr Formanowicz

Keyword(s):

Essential Hypertension ◽

Adaptive Immune System ◽

Low Grade ◽

Kinin System ◽

Reactive Protein ◽

Adaptive Immune ◽

Key Enzyme ◽

Kallikrein Kinin System ◽

Low Grade Inflammation

Recent studies have shown that the innate and adaptive immune system, together with low-grade inflammation, may play an important role in essential hypertension. In this work, to verify the importance of selected factors for the development of essential hypertension, we created a Petri net-based model and analyzed it. The analysis was based mainly on t-invariants, knockouts of selected fragments of the net and its simulations. The blockade of the renin-angiotensin (RAA) system revealed that the most significant effect on the emergence of essential hypertension has RAA activation. This blockade affects: (1) the formation of angiotensin II, (2) inflammatory process (by influencing C-reactive protein (CRP)), (3) the initiation of blood coagulation, (4) bradykinin generation via the kallikrein-kinin system, (5) activation of lymphocytes in hypertension, (6) the participation of TNF alpha in the activation of the acute phase response, and (7) activation of NADPH oxidase—a key enzyme of oxidative stress. On the other hand, we found that the blockade of the activation of the RAA system may not eliminate hypertension that can occur due to disturbances associated with the osmotically independent binding of Na in the interstitium. Moreover, we revealed that inflammation alone is not enough to trigger primary hypertension, but it can coexist with it. We believe that our research may contribute to a better understanding of the pathology of hypertension. It can help identify potential subprocesses, which blocking will allow better control of essential hypertension.

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