Why does inflammation persist: a dominant role for the stromal microenvironment?

Inflammatory responses occur within tissue microenvironments, with functional contributions from both haematopoietic (lymphocytic) cells and stromal cells (including macrophages and fibroblasts). These environments are complex – a compound of many different cell types at different stages of activation and differentiation. Traditional models of inflammatory disease highlight the role of antigen-specific lymphocyte responses and attempt to identify causative agents. However, recent studies have indicated the importance of tissue microenvironments and the innate immune response in perpetuating the inflammatory process. The prominent role of stromal cells in the generation and maintenance of these environments has begun to challenge the primacy of the lymphocyte in regulating chronic inflammatory processes. Sensible enquiries into factors regulating the persistence of inflammatory disease necessitate an understanding of the mechanisms regulating tissue homeostasis and remodelling during inflammation. This article highlights recent insights into the factors regulating dynamic aspects of inflammation, focusing particularly on mononuclear cell infiltrates, their interactions with stromal cells in tissues and the relevance of these interactions to existing and possible future therapies. A key feature of current research has been a growing appreciation that disordered spatial and temporal interactions between infiltrating immune cells and resident stromal cells lie at the heart of disease persistence.

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Nuclear receptor Nur77: its role in chronic inflammatory diseases

Essays in Biochemistry ◽

10.1042/ebc20210004 ◽

2021 ◽

Author(s):

Sanne C. Lith ◽

Carlie J.M. de Vries

Keyword(s):

Nuclear Receptor ◽

Inflammatory Disease ◽

Inflammatory Responses ◽

Current Knowledge ◽

Inflammatory Diseases ◽

Cell Types ◽

Experimental Models ◽

Therapeutic Interventions ◽

Alternative Mechanism ◽

Signaling Complex

Abstract Nur77 is a nuclear receptor that has been implicated as a regulator of inflammatory disease. The expression of Nur77 increases upon stimulation of immune cells and is differentially expressed in chronically inflamed organs in human and experimental models. Furthermore, in a variety of animal models dedicated to study inflammatory diseases, changes in Nur77 expression alter disease outcome. The available studies comprise a wealth of information on the function of Nur77 in diverse cell types and tissues. Negative cross-talk of Nur77 with the NFκB signaling complex is an example of Nur77 effector function. An alternative mechanism of action has been established, involving Nur77-mediated modulation of metabolism in macrophages as well as in T cells. In this review, we summarize our current knowledge on the role of Nur77 in atherosclerosis, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and sepsis. Detailed insight in the control of inflammatory responses will be essential in order to advance Nur77-targeted therapeutic interventions in inflammatory disease.

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Resveratrol suppresses inflammatory responses in endometrial stromal cells derived from endometriosis: A possible role of the sirtuin 1 pathway

Journal of Obstetrics and Gynaecology Research ◽

10.1111/jog.12252 ◽

2013 ◽

Vol 40 (3) ◽

pp. 770-778 ◽

Cited By ~ 28

Author(s):

Ayumi Taguchi ◽

Osamu Wada-Hiraike ◽

Kei Kawana ◽

Kaori Koga ◽

Aki Yamashita ◽

...

Keyword(s):

Stromal Cells ◽

Inflammatory Responses ◽

Sirtuin 1 ◽

Endometrial Stromal Cells

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Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration

Burns & Trauma ◽

10.1186/s41038-019-0178-8 ◽

2019 ◽

Vol 7 ◽

Cited By ~ 15

Author(s):

Peng Hu ◽

Qinxin Yang ◽

Qi Wang ◽

Chenshuo Shi ◽

Dali Wang ◽

...

Keyword(s):

Wound Healing ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Messenger Rna ◽

Cell Types ◽

Skin Wound ◽

Effector Proteins ◽

Skin Wound Healing ◽

New Research

Abstact Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types, growth factors, extracellular matrix (ECM), nerves, and blood vessels. Mesenchymal stromal cells (MSCs) take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans. Exosomes, which are among the key products MSCs release, mimic the effects of parental MSCs. They can shuttle various effector proteins, messenger RNA (mRNA) and microRNAs (miRNAs) to modulate the activity of recipient cells, playing important roles in wound healing. Moreover, using exosomes avoids many risks associated with cell transplantation. Therefore, as a novel type of cell-free therapy, MSC-exosome -mediated administration may be safer and more efficient than whole cell. In this review, we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration. In addition, we address the hypothesis of MSCs microenvironment extracellular vesicles (MSCs-MEVs) or MSCs microenvironment exosomes (MSCs-MExos) that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications. This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration.

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Immunocytochemical localization of oestrogen receptors in the endometrium of the ewe

Reproduction Fertility and Development ◽

10.1071/rd9910321 ◽

1991 ◽

Vol 3 (3) ◽

pp. 321 ◽

Cited By ~ 31

Author(s):

RA Cherny ◽

LA Salamonsen ◽

JK Findlay

Keyword(s):

Stromal Cells ◽

Cellular Response ◽

Individual Cell ◽

Cell Types ◽

Staining Intensity ◽

Steroid Treatment ◽

Positive Staining ◽

Cell Type ◽

Peak Intensity

Immunocytochemistry with monoclonal antibodies to the oestrogen receptor (ER) was used to localize ERs in sections of endometrium obtained from cycling and pregnant Corriedale ewes. Representative tissue from Days 4, 10, 14, 15, 16 and 17 of the cycle (Day 0 = onset of oestrus) and Day 15 of pregnancy was used. ER localization was also examined in tissue obtained from ovariectomized (ovex) ewes with and without subcutaneous implants containing oestrogen, progesterone, or oestrogen and progesterone. ER distribution was examined in caruncular endometrium and intercaruncular endometrium. Staining intensity varied according to cell type, stage of the cycle, steroid treatment and pregnancy. No staining was observed in endothelial cells. In all cases, ER was localized within the nuclei of positive cells. Generally, ER levels were high on Day 4 and declined to negligible values by Day 10 (corresponding to peak progesterone values) except in the deep stroma of caruncular endometrium. Positive staining reappeared in stromal cells of caruncles on Day 13 and in the luminal epithelium of intercaruncular tissue on Day 14. Peak intensity was reached on Day 15 for caruncular tissue and Day 16 for intercaruncular tissue. Ovariectomy did not cause an overall reduction in ER levels, whereas treatment with oestrogen and progesterone had variable effects depending on cell type. Progesterone did not suppress overall ER. In Day 15 pregnant tissue, ER was undetectable in all compartments except deep stroma of caruncles, indicating that factors other than progesterone, perhaps embryonic in origin, were responsible. The observation that individual cell types display differential sensitivities to oestrogen and progesterone as regards their expression of ER is consistent with the role of cell-cell interactions as modulators of cellular response to steroids through the oestrous cycle and in pregnancy.

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Non-Alcoholic Steatohepatitis: Clinical and Translational Research

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3f61f ◽

2016 ◽

Vol 19 (1) ◽

pp. 8 ◽

Cited By ~ 2

Author(s):

Manuela G Neuman ◽

Mihai Voiculescu ◽

Radu M Nanau ◽

Yaakov Maor ◽

Ehud Melzer ◽

...

Keyword(s):

Fatty Liver ◽

Liver Damage ◽

Immune Modulation ◽

Inflammatory Responses ◽

Cell Types ◽

Organ Injury ◽

Alcoholic Fatty Liver ◽

Neuropsychological Disorders ◽

Alcoholic Steatohepatitis

The present review includes translational and clinical research that characterize non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Clinical and experimental evidence led to the recognition of the key toxic role played by lipotoxicity in the pathogenesis of NAFLD. The current understanding of lipotoxicity suggests that organ injury is initiated by the generation of oxidative metabolites and the translocation of gut-derived endotoxin. These processes lead to cellular injury and stimulation of the inflammatory responses mediated through a variety of molecules. The injury progresses through impairment of tissue regeneration and extracellular matrix turnover, leading to fibrogenesis and cirrhosis. Several cell types are involved in this process, predominantly stellate cells, macrophages and parenchymal cells. In response to inflammation, cytokines activate many signaling cascades that regulate fibrogenesis. This examination brings together research focusing on the underlying mechanisms of injury. It highlights the various processes and molecules that are likely involved in inflammation, immune modulation, and fibrogenesis in the liver. We searched electronic databases (Medline, Embase) for this review. This integrative work investigates different aspects of liver damage and possible repair. We aim to (1) determine the immuno-pathology of liver damage due to steatosis, (2) suggest diagnostic markers of NASH, (3) examine the role of behaviour in the development of NASH, and (4) develop common tools to study steatosis-induced effects in clinical studies. Special accent is put on co-morbidities with renal and neuropsychological disorders. Moreover, we review the evidence in literature on the role of moderate alcohol consumption in individuals that present NAFLD/NASH.Key Words: behavior, diet, imaging, non-alcoholic fatty liver, nonalcoholic steatohepatitis, laboratory markers.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Phagocytosis in Mesocestoides vogae-induced peritoneal monocytes/macrophages via opsonin-dependent or independent pathways

Helminthologia ◽

10.1515/helmin-2015-0062 ◽

2016 ◽

Vol 53 (1) ◽

pp. 3-13 ◽

Cited By ~ 1

Author(s):

G. Hrčková ◽

E. Vendelova ◽

S. Velebný

Keyword(s):

Phagocytic Activity ◽

Inflammatory Responses ◽

Cell Types ◽

Phagocytic Cells ◽

Monocytic Cells ◽

Latex Beads ◽

Oral Inoculation ◽

Intraperitoneal Infection ◽

Mesocestoides Vogae

SummaryIntraperitoneal infection with larvae of cestode Mesocestoides vogae offers the opportunity to study dynamic changes in the proportion and functions of individual cell types under a direct influence of parasites. The phagocytic activity is one of the basic effector functions of professional phagocytes and receptor-mediated uptake is a central in implementation of inflammatory responses. Present study extends information on this issue by exploring several phagocytosis pathways in M. vogae-induced myelo-monocytic cells. In addition, we analyzed proportions of morphologically distinct phenotypes within macrophage compartments after oral inoculation of larvae to mice. In gradually elevated population of peritoneal exudate cells, monocytes/ macrophages and giant cell were dominant cell types from day 21 p.i. Phagocytic activity of these cells had biphasic behaviour for both opsonin-dependent and independent pathways, whereas uptake by multinucleated macrophages was profoundly reduced. Highly elevated proportions of activated phagocytic cells were found from day 7 to 14 p.i., regardless particle type (latex beads, HEMA, liposomes) and opsonisation. Source of opsonins used for coating of liposomes suggested higher expression of complement receptors than Fc receptors on these cells, although the uptake of non-opsonized liposomes had different kinetics and was very high by activated cells early p.i. Present data indicate that early recruited macrophages/monocytes attain pro-inflammatory functions as indicated by highly elevated phagocytosis of immunologically inert particles as well as opsonized liposomes what is down-regulated once larvae start to proliferate in the peritoneal cavity, suggesting the role of parasite-derived molecules in modulation of this key phagocytes function.

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The Role of IL-33 in Host Response toCandida albicans

The Scientific World JOURNAL ◽

10.1155/2014/340690 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

C. Rodríguez-Cerdeira ◽

A. Lopez-Bárcenas ◽

B. Sánchez-Blanco ◽

R. Arenas

Keyword(s):

Defense Mechanisms ◽

Fungal Pathogens ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Case Reports ◽

Pathogenic Fungi ◽

Cell Types ◽

Immune Defense ◽

Beneficial Role

Background. Interleukin (IL) 33 is a recently identified pleiotropic cytokine that influences the activity of multiple cell types and orchestrates complex innate and adaptive immune responses.Methods. We performed an extensive review of the literature published between 2005 and 2013 on IL-33 and related cytokines, their functions, and their regulation of the immune system followingCandida albicanscolonization. Our literature review included cross-references from retrieved articles and specific data from our own studies.Results. IL-33 (IL-1F11) is a recently identified member of the IL-1 family of cytokines. Accumulating evidence suggests a pivotal role of the IL-33/ST2 axis in host immune defense against fungal pathogens, includingC. albicans. IL-33 induces a Th2-type inflammatory response and activates both innate and adaptive immunity. Studies in animal models have shown that Th2 inflammatory responses have a beneficial role in immunity against gastrointestinal and systemic infections byCandidaspp.Conclusions. This review summarizes the most important clinical studies and case reports describing the beneficial role of IL-33 in immunity and host defense mechanisms against pathogenic fungi. The finding that the IL-33/ST2 axis is involved in therapeutic target has implications for the prevention and treatment of inflammatory diseases, including acute or chronic candidiasis.

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Putative positive role of inflammatory genes in fat deposition supported by altered gene expression in purified human adipocytes and preadipocytes from lean and obese adipose tissues

10.21203/rs.3.rs-15748/v1 ◽

2020 ◽

Author(s):

Sang-Hyeop Lee ◽

Nak-Hyeon Choi ◽

In-Uk Koh ◽

Bong-Jo Kim ◽

Song Lee ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Responses ◽

Cell Types ◽

Deposition Process ◽

Fat Deposition ◽

Low Grade ◽

Positive Role ◽

Inflammatory Genes ◽

Altered Gene

Abstract BackgroundObesity is a chronic low-grade inflammatory disease that is generally characterized by enhanced inflammation in obese adipose tissue (AT). Here, we investigated alterations in gene expression between lean and obese conditions using mRNA-Seq data derived from human purified adipocytes (ACs) and preadipocytes (preACs). ResultsWe defined four classes of differentially expressed genes (DEGs) by comparing gene expression between 1) lean and obese ACs, 2) lean and obese preACs, 3) lean ACs and lean preACs, and 4) obese ACs and obese preACs. Based on an analysis of comparison 1, numerous canonical obesity-related genes, particularly inflammatory genes including IL6, TNF- and IL-1, i.e., the genes that are expected to be upregulated in obesity conditions, were found to be expressed at significantly lower levels in obese ACs than in lean ACs. In contrast, some inflammatory genes were found to be expressed at higher levels in obese preACs than lean preACs in the analysis of comparison 2. These two results indicate that (1) up-/downregulation of genes in ACs and preACs is inversely controlled during the fat deposition process and (2) preACs rather than ACs have increased inflammatory response genes in comparisons of lean and obese conditions for each of these cell types. Analysis of comparisons 3 and 4 showed that inflammatory gene classes were expressed at higher levels in differentiated ACs than undifferentiated preACs under both lean and obese conditions; however, the degree of upregulation was greater for lean than for obese conditions.ConclusionsTaken together, our analyses may suggest that lean fat differentiation involves even greater enhancement of inflammatory responses than does obese fat differentiation.

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Critical role of microglia in the inflammatory response after spinal injury

American Journal of BioMedicine ◽

10.18081/2333-5106/015-03/453-462 ◽

2015 ◽

Vol 3 (3) ◽

pp. 453-462

Author(s):

Ya-Yun Shi

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Inflammatory Responses ◽

Spinal Injury ◽

Critical Role ◽

Cell Types ◽

Inflammatory Factors ◽

Cytokines And Chemokines ◽

Cord Injury

Spinal cord injury induces a robust neuroinflammatory response that includes marked changes in the variety of endogenous CNS cell types specially microglia. In response to spinal injury, microglia undergo dramatic changes in cell morphology and promote inflammatory responses, which result in production of inflammatory factors and oxidative stress including reactive oxygen species. Further pro-inflammatory cytokines and chemokines are also rapidly up-regulated and likely contribute to microglial activation. This topic review will explore the current research on microglial responses to spinal injury and the recent progress in the pharmacologic and molecular targeting of microglia in spinal injury. Finally, we explore the argument for a positive versus negative role of microglia after spinal cord injury.

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Lymphoid Tissue Mesenchymal Stromal Cells in Development and Tissue Remodeling

Stem Cells International ◽

10.1155/2016/8419104 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Luca Genovese ◽

Andrea Brendolan

Keyword(s):

Immune Responses ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Cell Activation ◽

Critical Role ◽

Tissue Remodeling ◽

Stromal Microenvironment ◽

Inflammatory Conditions ◽

Secondary Lymphoid Organs

Secondary lymphoid organs (SLOs) are sites that facilitate cell-cell interactions required for generating adaptive immune responses. Nonhematopoietic mesenchymal stromal cells have been shown to play a critical role in SLO function, organization, and tissue homeostasis. The stromal microenvironment undergoes profound remodeling to support immune responses. However, chronic inflammatory conditions can promote uncontrolled stromal cell activation and aberrant tissue remodeling including fibrosis, thus leading to tissue damage. Despite recent advancements, the origin and role of mesenchymal stromal cells involved in SLO development and remodeling remain unclear.

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