The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases

Chemokine is a structure-related protein with a relatively small molecular weight, which can target cells to chemotaxis and promote inflammatory response. Inflammation plays an important role in aging. C-C chemokine receptor 9 (CCR9) and its ligand C-C chemokine ligand 25 (CCL25) are involved in the regulating the occurrence and development of various diseases, which has become a research hotspot. Early research analysis of CCR9-deficient mouse models also confirmed various physiological functions of this chemokine in inflammatory responses. Moreover, CCR9/CCL25 has been shown to play an important role in a variety of inflammation-related diseases, such as cardiovascular disease (CVD), rheumatoid arthritis, hepatitis, inflammatory bowel disease, asthma, etc. Therefore, the purpose of this review gives an overview of the recent advances in understanding the roles of CCR9/CCL25 in inflammation and inflammation-associated diseases, which will contribute to the design of future experimental studies on the potential of CCR9/CCL25 and advance the research of CCR9/CCL25 as pharmacological inflammatory targets.

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CCR6–CCL20 Axis in IBD: What Have We Learnt in the Last 20 Years?

Gastrointestinal Disorders ◽

10.3390/gidisord1010006 ◽

2018 ◽

Vol 1 (1) ◽

pp. 57-74 ◽

Cited By ~ 3

Author(s):

Ranmali Ranasinghe ◽

Rajaraman Eri

Keyword(s):

Intestinal Inflammation ◽

Experimental Studies ◽

Protective Mechanisms ◽

Cc Chemokine ◽

Large Numbers ◽

Causative Factors ◽

Chemokine Ligand ◽

Disease Entities ◽

Inflammatory Bowel ◽

The Subject

CC chemokine receptor 6 (CCR6) and its specific partner CC chemokine ligand 20 (CCL20) are known to play a pivotal role in intestinal inflammation. CCR6-associated inflammatory bowel disease (IBD) is already at the forefront of experimental inflammatory disease models, being the subject of numerous analytical studies. IBD is associated with two sub phenotypes, Crohn’s disease (CD) and ulcerative colitis (UC). Both these disease entities produce potent immune dysregulation followed by intense tissue damage within the gut mucosal system, initiating symptoms that are severely debilitating. Multiple causative factors are said to be responsible for IBD, but direct immune dysfunction is kindled by overplay of innate and adaptive immune responses produced against the luminal contents through the weakened or leaky gut epithelial barrier. Once immune homeostasis is not achieved by endogenous protective mechanisms, the self-assertive adaptive immunity mobilizes its various T and B cell cohorts, initializing their immune mechanisms by deploying the immune cells towards the site of infection. CCR6 and its unique solitary ligand CCL20 are small protein molecules that are abundantly expressed by T and B lymphocytes and act as chemotactic immune-modulatory envoys that help in the deployment of the effector lymphocyte arm of the immune system and produce two directly opposing outcomes in IBD. This dichotomous immunity consists of either immune tolerance or inflammation which then develops into a chronic state, remaining unresponsive to inherent immunity or targeted clinical therapy. In this review, we have identified large numbers of experimental studies that have employed both mouse models and clinical subjects spanning a period of nearly two decades and we have clustered these into 13 different groups. This review will provide greater understanding of the CCR6–CCL20 axis in IBD and identify gaps in the literature that can be filled in the future.

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CCR6-CCL20 Axis in IBD: What have we learnt in the past 20 years?

10.20944/preprints201808.0381.v1 ◽

2018 ◽

Author(s):

Ranmali Ranasinghe ◽

Rajaraman Eri

Keyword(s):

Experimental Studies ◽

Cc Chemokine ◽

Adaptive Immune ◽

Immune Mediated ◽

Causative Factors ◽

Chemokine Ligand ◽

Disease Entities ◽

Inflammatory Bowel ◽

Visual Depiction ◽

Microbial Attack

Inflammatory bowel disease (IBD) is a CC chemokine receptor 6 (CCR6) - associated immune mediated disorder which has attracted an extensive superfluity of experimental analyses. IBD has come to the fore of varied scrutinizing owing to its complexity by nature for comprising of two synergistic sub phenotypes; Crohn’s disease (CD) and Ulcerative colitis (UC). Both these disease entities cause potent immune dysregulation followed by intense tissue damage within the gut mucosal system, initiating symptoms which are severely debilitating. Multiple causative factors are said to be responsible for IBD but direct immune dysfunction is kindled by overplay of innate and adaptive immune responses produced against a pathogenic microbial attack through the weakened or leaky gut epithelial barrier. Once immune homeostasis is not achieved by tolerating agents, the self-assertive adaptive immunity mobilize its various T and B cell cohorts initializing their allied immune mechanisms by vigorously deploying them towards the site of infection. CCR6 and its unique solitary ligand CC-chemokine ligand 20 (CCL20) are small protein molecules which are abundantly expressed by T and B lymphocytes and act as chemotactic immune-modulatory envoys that help in the deployment of the effector lymphocyte arm of the immune system, producing two directly opposing outcomes in IBD. This dichotomous immunity consists of either immune tolerance or inflammation which then develops into a chronic state, remaining catatonic to inherent immunity or targeted clinical therapy. In this review, we have chronologically identified a plethora of experimental studies radiating into 14 different compartments highlighted in the visual depiction which have employed both mouse models and clinical subjects spanning a period of nearly two decades. In doing so, we expect the research community would further benefit by tracing through the history, thereby understanding the CCR6 –CCL20 axis in IBD and identifying the gaps in literature which can be fortuitously filled in the future.

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Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00803-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Lu Wang ◽

Yafei Rao ◽

Xiali Liu ◽

Liya Sun ◽

Jiameng Gong ◽

...

Keyword(s):

Therapeutic Efficacy ◽

Lung Inflammation ◽

Respiratory Diseases ◽

Inflammatory Responses ◽

The Other ◽

Target Cells ◽

Administration Route ◽

Toll Like Receptor ◽

Administration Routes ◽

Anti Inflammatory

Abstract Background Uncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined. Results In this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthermore, the inflammatory condition in the lung could decrease the accumulation of nanoparticles in the lung and liver, while increasing their distribution in the spleen and heart. Interestingly, the i.t. administration route helped the nanoparticles specifically target the lung macrophages, whereas the other two administration routes did not. Conclusion The i.t. administration is better for treating ALI using nanodevices as it enhances the bioavailability and efficacy of the nanodrugs in the target cells of the lung and reduces the potential systematic side effects.

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Significance of African Diets in Biotherapeutic Modulation of the Gut Microbiome

Bioinformatics and Biology Insights ◽

10.1177/11779322211012697 ◽

2021 ◽

Vol 15 ◽

pp. 117793222110126

Author(s):

PO Isibor ◽

PA Akinduti ◽

OS Aworunse ◽

JO Oyewale ◽

O Oshamika ◽

...

Keyword(s):

Type 2 Diabetes ◽

Immune Cell ◽

Inflammatory Responses ◽

Brown Rice ◽

Well Being ◽

Population Characteristics ◽

Sub Saharan Africa ◽

Bowel Diseases ◽

Inflammatory Bowel

Diet plays an essential role in human development and growth, contributing to health and well-being. The socio-economic values, cultural perspectives, and dietary formulation in sub-Saharan Africa can influence gut health and disease prevention. The vast microbial ecosystems in the human gut frequently interrelate to maintain a healthy, well-coordinated cellular and humoral immune signalling to prevent metabolic dysfunction, pathogen dominance, and induction of systemic diseases. The diverse indigenous diets could differentially act as biotherapeutics to modulate microbial abundance and population characteristics. Such modulation could prevent stunted growth, malnutrition, induction of bowel diseases, attenuated immune responses, and mortality, particularly among infants. Understanding the associations between specific indigenous African diets and the predictability of the dynamics of gut bacteria genera promises potential biotherapeutics towards improving the prevention, control, and treatment of microbiome-associated diseases such as cancer, inflammatory bowel disease, obesity, type 2 diabetes, and cardiovascular disease. The dietary influence of many African diets (especially grain-base such as millet, maize, brown rice, sorghum, soya, and tapioca) promotes gut lining integrity, immune tolerance towards the microbiota, and its associated immune and inflammatory responses. A fibre-rich diet is a promising biotherapeutic candidate that could effectively modulate inflammatory mediators’ expression associated with immune cell migration, lymphoid tissue maturation, and signalling pathways. It could also modulate the stimulation of cytokines and chemokines involved in ensuring balance for long-term microbiome programming. The interplay between host and gut microbial digestion is complex; microbes using and competing for dietary and endogenous proteins are often attributable to variances in the comparative abundances of Enterobacteriaceae taxa. Many auto-inducers could initiate the process of quorum sensing and mammalian epinephrine host cell signalling system. It could also downregulate inflammatory signals with microbiota tumour taxa that could trigger colorectal cancer initiation, metabolic type 2 diabetes, and inflammatory bowel diseases. The exploitation of essential biotherapeutic molecules derived from fibre-rich indigenous diet promises food substances for the downregulation of inflammatory signalling that could be harmful to gut microbiota ecological balance and improved immune response modulation.

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Can We Target Endogenous Anti-inflammatory Responses as a Therapeutic Strategy for Inflammatory Bowel Disease?

Inflammatory Bowel Diseases ◽

10.1093/ibd/izy230 ◽

2018 ◽

Vol 24 (10) ◽

pp. 2123-2134 ◽

Cited By ~ 2

Author(s):

Ross John Porter ◽

Caroline Andrews ◽

Daniel Paul Brice ◽

Scott Kenneth Durum ◽

Mairi Hall McLean

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Therapeutic Strategy ◽

Inflammatory Responses ◽

Inflammatory Bowel ◽

Anti Inflammatory

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Selye’s general adaptation syndrome: stress-induced gastro-duodenal ulceration and inflammatory bowel disease

Journal of Endocrinology ◽

10.1530/joe-16-0547 ◽

2017 ◽

Vol 232 (3) ◽

pp. F1-F5 ◽

Cited By ~ 4

Author(s):

George Fink

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Experimental Studies ◽

Peptic Ulceration ◽

Duodenal Ulceration ◽

Peptic Ulcers ◽

General Adaptation Syndrome ◽

General Adaptation ◽

Inflammatory Bowel ◽

H Pylori

Hans Selye in a note to Nature in 1936 initiated the field of stress research by showing that rats exposed to nocuous stimuli responded by way of a ‘general adaptation syndrome’ (GAS). One of the main features of the GAS was the ‘formation of acute erosions in the digestive tract, particularly in the stomach, small intestine and appendix’. This provided experimental evidence for the view based on clinical data that gastro-duodenal (peptic) ulcers could be caused by stress. This hypothesis was challenged by Marshall and Warren’s Nobel Prize (2005)-winning discovery of a causal association between Helicobacter pylori and peptic ulcers. However, clinical and experimental studies suggest that stress can cause peptic ulceration in the absence of H. pylori. Predictably, the etiological pendulum of gastric and duodenal ulceration has swung from ‘all stress’ to ‘all bacteria’ followed by a sober realization that both factors play a role, separately as well as together. This raises the question as to whether stress and H. pylori interact, and if so, how? Stress has also been implicated in inflammatory bowel disease (IBD) and related disorders; however, there is no proof yet that stress is the primary etiological trigger for IBD. Central dopamine mechanisms seem to be involved in the stress induction of peptic ulceration, whereas activation of the sympathetic nervous system and central and peripheral corticotrophin-releasing factor appears to mediate stress-induced IBD.

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P2X7 Receptor–Mediated Inflammation in Cardiovascular Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.654425 ◽

2021 ◽

Vol 12 ◽

Author(s):

Junteng Zhou ◽

Zhichao Zhou ◽

Xiaojing Liu ◽

Hai-Yan Yin ◽

Yong Tang ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cardiovascular Diseases ◽

P2x7 Receptor ◽

Cardiac Fibrosis ◽

Inflammatory Responses ◽

Interleukin 1 ◽

Experimental Studies ◽

Therapeutic Interventions ◽

Receptor Protein ◽

Inflammasome Activation

Purinergic P2X7 receptor, a nonselective cation channel, is highly expressed in immune cells as well as cardiac smooth muscle cells and endothelial cells. Its activation exhibits to mediate nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome activation, resulting in the release of interleukin-1 beta (IL-1β) and interleukin-18 (IL-18), and pyroptosis, thus triggering inflammatory response. These pathological mechanisms lead to the deterioration of various cardiovascular diseases, including atherosclerosis, arrhythmia, myocardial infarction, pulmonary vascular remodeling, and cardiac fibrosis. All these worsening cardiac phenotypes are proven to be attenuated after the P2X7 receptor inhibition in experimental studies. The present review aimed to summarize key aspects of P2X7 receptor–mediated inflammation and pyroptosis in cardiovascular diseases. The main focus is on the evidence addressing the involvement of the P2X7 receptor in the inflammatory responses to the occurrence and development of cardiovascular disease and therapeutic interventions.

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Histamine receptors as drug target: Current and future therapeutics.

Journal of Shifa Tameer-e-Millat University ◽

10.32593/jstmu/vol2.iss1.25 ◽

2019 ◽

Vol 2 (1) ◽

pp. 31-35 ◽

Cited By ~ 1

Author(s):

Atteqa Jawad ◽

Richa Kaushal ◽

Muhammad Sohail ◽

Amna Yaqoob

Keyword(s):

Drug Target ◽

Inflammatory Responses ◽

Experimental Studies ◽

Gastric Ulcers ◽

Central Regulation ◽

Inflammatory Reactions ◽

Central Effects ◽

Memory Modulation ◽

Gastric Secretions

Histamine is a neurotransmitter responsible for central regulation of inflammatory reactions. Initial studies were done by Sir Henry Dale in 1993. Histamine acts on its four type of receptors. H1 and H2 are well-established with pharmacological status. H1 receptors are mainly linked with inflammatory responses and developed to mitigate the inflammatory symptoms. While H2 antagonists are established with their role in decreasing basal gastric secretions by decreasing the cyclic adenylyl mono phosphate (cAMP), thus used as therapy line for gastric ulcers. H3 being located centrally imparts its central effects in cognitive functions that are pain, sleep, and memory modulation of neurotransmitters release including, dopamine, acetylcholine, noradrenalin and serotonin. H4 is discovered recently during cloning of H3 and found on immune related cells as, mast cells, T cells and dendrites. Experimental studies are helping in development of more pharmacologically worth drugs that can increase the quality of life.

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Activation of PTH1R alleviates epididymitis and orchitis through Gq and β-arrestin-1 pathways

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2107363118 ◽

2021 ◽

Vol 118 (45) ◽

pp. e2107363118

Author(s):

Ming-Wei Wang ◽

Zhao Yang ◽

Xu Chen ◽

Shu-Hua Zhou ◽

Ge-Lin Huang ◽

...

Keyword(s):

Parathyroid Hormone ◽

Leydig Cells ◽

Inflammatory Responses ◽

Mumps Virus ◽

Related Protein ◽

Parathyroid Hormone Receptor ◽

Current Therapies ◽

G Protein Coupled ◽

Sperm Functions

Inflammation in the epididymis and testis contributes significantly to male infertility. Alternative therapeutic avenues treating epididymitis and orchitis are expected since current therapies using antibiotics have limitations associated to side effects and are commonly ineffective for inflammation due to nonbacterial causes. Here, we demonstrated that type 1 parathyroid hormone receptor (PTH1R) and its endogenous agonists, parathyroid hormone (PTH) and PTH-related protein (PTHrP), were mainly expressed in the Leydig cells of testis as well as epididymal epithelial cells. Screening the secretin family G protein–coupled receptor identified that PTH1R in the epididymis and testis was down-regulated in mumps virus (MuV)- or lipopolysaccharide (LPS)-induced inflammation. Remarkably, activation of PTH1R by abaloparatide (ABL), a Food and Drug Administration–approved treatment for postmenopausal osteoporosis, alleviated MuV- or LPS-induced inflammatory responses in both testis and epididymis and significantly improved sperm functions in both mouse model and human samples. The anti-inflammatory effects of ABL were shown to be regulated mainly through the Gq and β-arrestin-1 pathway downstream of PTH1R as supported by the application of ABL in Gnaq± and Arrb1−/− mouse models. Taken together, our results identified an important immunoregulatory role for PTH1R signaling in the epididymis and testis. Targeting to PTH1R might have a therapeutic effect for the treatment of epididymitis and orchitis or other inflammatory disease in the male reproductive system.

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Can Plant Phenolic Compounds Protect the Skin from Airborne Particulate Matter?

Antioxidants ◽

10.3390/antiox8090379 ◽

2019 ◽

Vol 8 (9) ◽

pp. 379 ◽

Cited By ~ 8

Author(s):

Yong Chool Boo

Keyword(s):

Particulate Matter ◽

Phenolic Compounds ◽

Skin Diseases ◽

Inflammatory Responses ◽

Acne Vulgaris ◽

Experimental Studies ◽

Airborne Particulate Matter ◽

Skin Aging ◽

Atmospheric Environment ◽

Airborne Particulate

The skin is directly exposed to the polluted atmospheric environment, and skin diseases, such as atopic dermatitis and acne vulgaris, can be induced or exacerbated by airborne particulate matter (PM). PM can also promote premature skin aging with its accompanying functional and morphological changes. PM-induced skin diseases and premature skin aging are largely mediated by reactive oxygen species (ROS), and the harmful effects of PM may be ameliorated by safe and effective natural antioxidants. Experimental studies have shown that the extracts and phenolic compounds derived from many plants, such as cocoa, green tea, grape, pomegranate, and some marine algae, have antioxidant and anti-inflammatory effects on PM-exposed cells. The phenolic compounds can decrease the levels of ROS in cells and/or enhance cellular antioxidant capacity and, thereby, can attenuate PM-induced oxidative damage to nucleic acids, proteins, and lipids. They also lower the levels of cytokines, chemokines, cell adhesion molecules, prostaglandins, and matrix metalloproteinases implicated in cellular inflammatory responses to PM. Although there is still much research to be done, current studies in this field suggest that plant-derived phenolic compounds may have a protective effect on skin exposed to high levels of air pollution.

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