Obesity and asthma: lessons from animal models

2007 ◽  
Vol 102 (2) ◽  
pp. 516-528 ◽  
Author(s):  
Stephanie A. Shore
Keyword(s):  
Epidemiological Data ◽  
Therapeutic Strategies ◽  
Murine Models ◽  
Asthmatic Subject ◽  
Tnf Α ◽  
Mechanical Factors ◽  
Mechanistic Basis ◽  
Novel Therapeutic Strategies ◽  
The Relationship

Epidemiological data indicate that obesity is a risk factor for asthma. These data are supported by observations in several murine models of obesity. Ob/ob, db/db, and Cpefatmice each exhibit innate airway hyperresponsiveness, a characteristic feature of asthma. These mice also respond more vigorously to common asthma triggers, including ozone. Here we discuss the implications of these data with respect to several mechanisms proposed to explain the relationship between obesity and asthma: 1) common etiologies; 2) comorbidities; 3) mechanical factors; and 4) adipokines. We focus on the role of adipokines, especially TNF-α, IL-6, leptin, and adiponectin. Understanding the mechanistic basis for the relationship between obesity and asthma may lead to novel therapeutic strategies for treatment of the obese asthmatic subject.

scholarly journals Obesity, airway hyperresponsiveness, and inflammation

2010 ◽  
Vol 108 (3) ◽  
pp. 735-743 ◽  
Author(s):  
Stephanie A. Shore
Keyword(s):  
Adipose Tissue ◽  
Airway Hyperresponsiveness ◽  
Human Subjects ◽  
Epidemiological Data ◽  
Asthmatic Subject ◽  
Adipose Tissue Macrophages ◽  
Tnf Α ◽  
Mechanistic Basis ◽  
Novel Therapeutic Strategies ◽  
The Relationship

Epidemiological data indicate that obesity is a risk factor for asthma, but the mechanistic basis for this relationship is not established. Here we review data from human subjects and animal models investigating the relationship between obesity and airway hyperresponsiveness, a characteristic feature of asthma. We discuss obesity as a state of chronic systemic inflammation resulting from interactions between adipocytes and adipose tissue macrophages that are recruited to obese adipose tissue. Finally, we focus on the possibility that aspects of this inflammation, particularly obesity-related changes in TNF-α, leptin, and adiponectin, may contribute to airway hyperresponsiveness in obesity. Determining how obesity promotes asthma may uncover novel therapeutic strategies that are effective in the obese asthmatic subject.

scholarly journals Eosinophil peroxidase induces inflammation in a mouse model of dermatitis

2020 ◽  
Author(s):  
Quinn R. Roth-Carter ◽  
Huijun Luo ◽  
Sergei I. Ochkur ◽  
Elizabeth A. Jacobsen ◽  
Meredith Datena ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lysophosphatidic Acid ◽  
Therapeutic Strategies ◽  
Trimellitic Anhydride ◽  
Important Mediator ◽  
Eosinophil Peroxidase ◽  
Tnf Α ◽  
Eosinophil Granule ◽  
Novel Therapeutic Strategies

ABSTRACTEosinophils play an important role in mediating itch and inflammation in dermatitis. The role of the eosinophil granule protein eosinophil peroxidase (EPX) in mediating inflammation and itch was tested in a dermatitis mouse model. Mice were sensitized to trimellitic anhydride (TMA) and subsequently challenged chronically on the ear to establish dermatitis. Loss of EPX (in EPX (-/-) mice) or blocking EPX with the drug resorcinol significantly reduced dermatitis in mice exposed to TMA. Resorcinol also reduced levels of thymic stromal lymphopoietin protein (TSLP) in skin. Further studies showed that EPX increased different cytokines in keratinocytes in cell culture via two distinct mechanisms. EPX induced TSLP expression requires lysophosphatidic acid signaling while EPX induced expression of TNF-α, CSF2, CSF3, and IL1α required IL-1 signaling. We also showed that blocking IL-1 reduced inflammation in skin following TMA exposure in mice. Thus, EPX is an important mediator of inflammation and itch, that are mediated via at least two pathways. This suggests that both EPX and its’ signaling pathways may provide novel therapeutic strategies in dermatitis.

Is Immune Response Relevant in Interstitial Lung Disease?

2020 ◽  
Vol 16 (1) ◽  
pp. 18-27
Author(s):  
Manzoor M. Khan
Keyword(s):  
Immune Response ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Lung Fibrosis ◽  
Lymphocytic Infiltration ◽  
Therapeutic Strategies ◽  
Mediators Of Inflammation ◽  
Acquired Immune Responses ◽  
Novel Therapeutic Strategies

Interstitial lung disease, a term for a group of disorders, causes lung fibrosis, is mostly refractory to treatments and has a high death rate. After diagnosis the survival is up to 3 years but in some cases the patients live much longer. It involves a heterogenous group of lung diseases that exhibit progressive and irreversible destruction of the lung due to the formation of scars. This results in lung malfunction, disruption of gas exchange, and eventual death because of respiratory failure. The etiology of lung fibrosis is mostly unknown with a few exceptions. The major characteristics of the disease are comprised of injury of epithelial type II cells, increased apoptosis, chronic inflammation, monocytic and lymphocytic infiltration, accumulation of myofibroblasts, and inability to repair damaged tissue properly. These events result in abnormal collagen deposition and scarring. The inflammation process is mild, and the disease is primarily fibrotic driven. Immunosuppressants do not treat the disease but the evidence is evolving that both innate and acquired immune responses a well as the cytokines contribute to at least early progression of the disease. Furthermore, mediators of inflammation including cytokines are involved throughout the process of lung fibrosis. The diverse clinical outcome of the disease is due to different pattern of inflammatory markers. Nonetheless, the development of novel therapeutic strategies requires better understanding of the role of the immune response. This review highlights the role of the immune response in interstitial lung disease and considers the therapeutic strategies based on these observations. For this review several literature data sources were used to assess the role of the immune response in interstitial lung disease and to evaluate the possible therapeutic strategies for the disease.

scholarly journals Skin and Gut Microbiome in Psoriasis: Gaining Insight Into the Pathophysiology of It and Finding Novel Therapeutic Strategies

2020 ◽  
Vol 11 ◽  
Author(s):  
Lihui Chen ◽  
Jie Li ◽  
Wu Zhu ◽  
Yehong Kuang ◽  
Tao Liu ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Therapeutic Strategies ◽  
Intestinal Microbiome ◽  
Core Microbiome ◽  
The Core ◽  
The World ◽  
Novel Therapeutic Strategies ◽  
Insight Into ◽  
Gaining Insight

Psoriasis affects the health of myriad populations around the world. The pathogenesis is multifactorial, and the exact driving factor remains unclear. This condition arises from the interaction between hyperproliferative keratinocytes and infiltrating immune cells, with poor prognosis and high recurrence. Better clinical treatments remain to be explored. There is much evidence that alterations in the skin and intestinal microbiome play an important role in the pathogenesis of psoriasis, and restoration of the microbiome is a promising preventive and therapeutic strategy for psoriasis. Herein, we have reviewed recent studies on the psoriasis-related microbiome in an attempt to confidently identify the “core” microbiome of psoriasis patients, understand the role of microbiome in the pathogenesis of psoriasis, and explore new therapeutic strategies for psoriasis through microbial intervention.

Potential Role of Gut Microbiota in ALS Pathogenesis and Possible Novel Therapeutic Strategies

2018 ◽  
Vol 52 ◽  
pp. S68-S70 ◽  
Author(s):  
Letizia Mazzini ◽  
Luca Mogna ◽  
Fabiola De Marchi ◽  
Angela Amoruso ◽  
Marco Pane ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Potential Role ◽  
Therapeutic Strategies ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

scholarly journals Lymphangiogenesis in kidney and lymph node mediates renal inflammation and fibrosis

2019 ◽  
Vol 5 (6) ◽  
pp. eaaw5075 ◽  
Author(s):  
Guangchang Pei ◽  
Ying Yao ◽  
Qian Yang ◽  
Meng Wang ◽  
Yuxi Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Lymph Node ◽  
Lymphatic Vessels ◽  
Therapeutic Strategies ◽  
Lymphatic Endothelium ◽  
Chemokine Ligand ◽  
Novel Therapeutic Strategies ◽  
Draining Lymph Nodes ◽  
Novel Therapeutic

Lymphangiogenesis is associated with chronic kidney disease (CKD) and occurs following kidney transplant. Here, we demonstrate that expanding lymphatic vessels (LVs) in kidneys and corresponding renal draining lymph nodes (RDLNs) play critical roles in promoting intrarenal inflammation and fibrosis following renal injury. Our studies show that lymphangiogenesis in the kidney and RDLN is driven by proliferation of preexisting lymphatic endothelium expressing the essential C-C chemokine ligand 21 (CCL21). New injury-induced LVs also express CCL21, stimulating recruitment of more CCR7+dendritic cells (DCs) and lymphocytes into both RDLNs and spleen, resulting in a systemic lymphocyte expansion. Injury-induced intrarenal inflammation and fibrosis could be attenuated by blocking the recruitment of CCR7+cells into RDLN and spleen or inhibiting lymphangiogenesis. Elucidating the role of lymphangiogenesis in promoting intrarenal inflammation and fibrosis provides a key insight that can facilitate the development of novel therapeutic strategies to prevent progression of CKD-associated fibrosis.

scholarly journals Autophagy Intertwines with Different Diseases—Recent Strategies for Therapeutic Approaches

Diseases ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 15 ◽  
Author(s):  
Janani Ramesh ◽  
Larance Ronsard ◽  
Anthony Gao ◽  
Bhuvarahamurthy Venugopal
Keyword(s):  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Open Reading Frames ◽  
Signaling Cascades ◽  
Progression Rate ◽  
Therapeutic Approaches ◽  
Genes Encoding ◽  
Novel Therapeutic Strategies ◽  
Reading Frames

Autophagy is a regular and substantial “clear-out process” that occurs within the cell and that gets rid of debris that accumulates in membrane-enclosed vacuoles by using enzyme-rich lysosomes, which are filled with acids that degrade the contents of the vacuoles. This machinery is well-connected with many prevalent diseases, including cancer, HIV, and Parkinson’s disease. Considering that autophagy is well-known for its significant connections with a number of well-known fatal diseases, a thorough knowledge of the current findings in the field is essential in developing therapies to control the progression rate of diseases. Thus, this review summarizes the critical events comprising autophagy in the cellular system and the significance of its key molecules in manifesting this pathway in various diseases for down- or upregulation. We collectively reviewed the role of autophagy in various diseases, mainly neurodegenerative diseases, cancer, inflammatory diseases, and renal disorders. Here, some collective reports on autophagy showed that this process might serve as a dual performer: either protector or contributor to certain diseases. The aim of this review is to help researchers to understand the role of autophagy-regulating genes encoding functional open reading frames (ORFs) and its connection with diseases, which will eventually drive better understanding of both the progression and suppression of different diseases at various stages. This review also focuses on certain novel therapeutic strategies which have been published in the recent years based on targeting autophagy key proteins and its interconnecting signaling cascades.

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