Essential role of EP3 subtype in prostaglandin E2-induced adhesion of mouse cultured and peritoneal mast cells to the Arg-Gly-Asp-enriched matrix

2008 ◽  
Vol 295 (5) ◽  
pp. C1427-C1433 ◽  
Author(s):  
Mariko Sakanaka ◽  
Satoshi Tanaka ◽  
Yukihiko Sugimoto ◽  
Atsushi Ichikawa
Keyword(s):  
Mast Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Critical Role ◽  
Pivotal Role ◽  
Receptor Subtypes ◽  
Inflammatory Conditions ◽  
Peritoneal Mast Cells ◽  
Line P

Accumulating evidence has indicated that mast cells can modulate a wide variety of immune responses. Migration and adhesion play a critical role in regulation of tissue mast cell function, in particular, under inflammatory conditions. We previously demonstrated that prostaglandin (PG) E2 stimulates adhesion of a mouse mastocytoma cell line, P-815, to the Arg-Gly-Asp (RGD)-enriched matrix through cooperation between two PGE2 receptor subtypes: EP3 and EP4 (Hatae N, Kita A, Tanaka S, Sugimoto Y, Ichikawa A. J Biol Chem 278: 17977–17981, 2003). We here investigated PGE2-induced adhesion of IL-3-dependent bone marrow-derived cultured mast cells (BMMCs). In contrast to the elevated cAMP-dependent adhesion of P-815 cells, EP3-mediated Ca2+ mobilization plays a pivotal role in PGE2-induced adhesion of BMMCs. Adhesion and Ca2+ mobilization induced by PGE2 were abolished in the Ptger3−/− BMMCs and were significantly suppressed by treatment with pertussis toxin, a phospholipase C inhibitor, U-73122, and a store-operated Ca2+ channel inhibitor, SKF 36965, indicating the involvement of Gi-mediated Ca2+ influx. We then investigated PGE2-induced adhesion of peritoneal mast cells to the RGD-enriched matrix. EP3 subtype was found to be the dominant PGE receptor that expresses in mouse peritoneal mast cells. PGE2 induced adhesion of the peritoneal mast cells of the Ptger3+/+ mice, but not that of the Ptger3−/− mice. In rat peritoneal mast cells, PGE2 or an EP3 agonist stimulated both Ca2+ mobilization and adhesion to the RGD-enriched matrix. These results suggested that the EP3 subtype plays a pivotal role in PGE2-induced adhesion of murine mast cells to the RGD-enriched matrix through Ca2+ mobilization.

scholarly journals Lymphoid Tissue Mesenchymal Stromal Cells in Development and Tissue Remodeling

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
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.

scholarly journals Diacylglycerol metabolism in mast cells: a potential role in membrane fusion and arachidonic acid release.

1979 ◽  
Vol 150 (4) ◽  
pp. 1039-1044 ◽  
Author(s):  
D A Kennerly ◽  
T J Sullivan ◽  
P Sylwester ◽  
C W Parker
Keyword(s):  
Mast Cell ◽  
Arachidonic Acid ◽  
Mast Cells ◽  
Membrane Fusion ◽  
Cell Function ◽  
Fold Increase ◽  
Peritoneal Mast Cells ◽  
Acid Release ◽  
Precise Role

Purified rat peritoneal mast cells stimulated with the polycationic histamine-releasing agent compound 48/80 demonstrated a two- to four-fold increase in cellular levels of 1,2-diacylglycerol (DAG) within 1 min as detected by radioactive labeling and direct quantitation experiments. When 2-[1-14C]arachidonoyl-DAG was incubated in the presence of mast-cell homogenates, a rapid conversion to free arachidonate, and to a lesser extent, to monoacylglycerol, triglyceride, and phospholipid was observed. The release of arachidonate was proportional to the amount of broken-cell preparation added and the time of incubation, was prevented by preheating mast-cell preparations, and did not occur when 1-[1-14C]arachidonoyl-phosphatidylcholine was used as substrate, suggesting that the degradation was mediated by an enzyme with Dag-lipase activity. Although much work remains to be done to clarify the precise role of DAG in mast cells, DAG metabolism may be involved in secretion by generating substances which may faciliate membrane fusion and also in arachidonic acid-derived mediator formation by liberating esterified arachidonic acid from mast-cell lipids. Taken together, these studies indicate that the formation of DAG may play a central role in mast-cell function.

scholarly journals Ubiquitous Overexpression of Chromatin Remodeling Factor SRG3 Exacerbates Atopic Dermatitis in NC/Nga Mice by Enhancing Th2 Immune Responses

2021 ◽  
Vol 22 (4) ◽  
pp. 1553
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Jungmin Jeon ◽  
Yun Hoo Park ◽  
Tae-Cheol Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cells ◽  
Immune Responses ◽  
Chromatin Remodeling ◽  
Skin Diseases ◽  
Immunoglobulin E ◽  
Critical Role ◽  
Interleukin 4 ◽  
Inflammatory Skin Diseases ◽  
Immune Disorder

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3β-actin mice). We found that SRG3β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.

scholarly journals Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses

2012 ◽  
Vol 109 (40) ◽  
pp. E2699-E2706 ◽  
Author(s):  
R. Ouchida ◽  
H. Mori ◽  
K. Hase ◽  
H. Takatsu ◽  
T. Kurosaki ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Cell Survival ◽  
Critical Role ◽  
Fc Receptor ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
B Cell Survival

Abstract 636: Gut Microflora Influences Pathology in the Kawasaki Disease (KD) Vasculitis Mouse Model

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Daiko Wakita ◽  
Yosuke Kurashima ◽  
Yoshihiro Takasato ◽  
Youngho Lee ◽  
Kenichi Shimada ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immune Responses ◽  
Critical Role ◽  
Gut Microflora ◽  
Vascular Abnormalities ◽  
Coronary Arteritis ◽  
Specific Pathogen ◽  
New Perspective ◽  
Bacteria And Fungi

Background: KD is the leading cause of acquired heart disease in the US. We have demonstrated the critical role of innate immune responses via IL-1R/MyD88 signaling in the Lactobacillus casei cell wall extract (LCWE)-induced KD mouse model. The diversity and composition of microflora (both bacterial and fungal) have been associated with the regulation and alterations of immune responses and various pathologies. However, the role of gut microbiota in immunopathology of KD has not been investigated. Objective: To evaluate the role of gut microflora in development of coronary arteritis, and vascular abnormalities in KD mouse model. Methods and Results: We investigated the role of gut microflora in the LCWE-induced KD mouse model, using Specific-Pathogen Free (SPF) and Germ Free (GF) mice (C57BL/6). GF mice showed a significant decrease of KD lesions, including coronary arteritis compared with SPF mice. The development of LCWE-induced AAA, which we recently discovered in this mouse model, was also markedly diminished in GF mice. In addition to GF mice, we also investigated the specific role of commensal bacteria and/or fungi, and determined whether altered microorganism burden in this KD mouse model contributes to disease severity. To deplete bacteria and/or fungi in the gut microflora, we exposed pregnant SPF mice and their offspring to antibiotics cocktail (Abx) or antifungal drug (fluconazole; Fluc) in their drinking water for 5 wks and induced KD. The mice treated with Abx or Fluc had significantly reduced coronary arteritis and AAA compared to controls. The Abx plus Fluc administration showed marked decrease of KD vasculitis. Conclusions: We demonstrate here that gut microflora play a critical role in the development of KD vasculitis in LCWE-induced mouse model. Our results suggest that both bacteria and fungi in the intestinal microbiota may control the induction and severity of KD vasculitis. These findings provide a new perspective on the potential role of the microbiome in KD pathogenesis and may offer new diagnostic and therapeutic strategies for KD patients.

377 - Critical Role of TOB1 in Controlling Intestinal Mucosal Inflammation by Inhibitiing Th1/Th17 Immune Responses in IBD

2018 ◽  
Vol 154 (6) ◽  
pp. S-89
Author(s):  
Caiyun Ma ◽  
Cui Zhang ◽  
Wei Wu ◽  
Mingming Sun ◽  
Zhanju Liu
Keyword(s):  
Immune Responses ◽  
Critical Role ◽  
Mucosal Inflammation

scholarly journals Emerging Role of Exosomes in Tuberculosis: From Immunity Regulations to Vaccine and Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yin-Fu Sun ◽  
Jiang Pi ◽  
Jun-Fa Xu
Keyword(s):  
Immune Responses ◽  
Delivery System ◽  
Immune Modulation ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Communication ◽  
Immune Defense ◽  
Research Progress ◽  
Recent Research Progress

Exosomes are cell-derived nanovesicles carrying protein, lipid, and nucleic acid for secreting cells, and act as significant signal transport vectors for cell-cell communication and immune modulation. Immune-cell-derived exosomes have been found to contain molecules involved in immunological pathways, such as MHCII, cytokines, and pathogenic antigens. Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most fatal infectious diseases. The pathogen for tuberculosis escapes the immune defense and continues to replicate despite rigorous and complicate host cell mechanisms. The infected-cell-derived exosomes under this circumstance are found to trigger different immune responses, such as inflammation, antigen presentation, and activate subsequent pathways, highlighting the critical role of exosomes in anti-MTB immune response. Additionally, as a novel kind of delivery system, exosomes show potential in developing new vaccination and treatment of tuberculosis. We here summarize recent research progress regarding exosomes in the immune environment during MTB infection, and further discuss the potential of exosomes as delivery system for novel anti-MTB vaccines and therapies.

scholarly journals Role of Microbiome in Rheumatic Diseases

2017 ◽  
Vol 17 (2) ◽  
pp. 58-63 ◽  
Author(s):  
Chi Kit Au ◽  
Tin Lok Lai ◽  
Cheuk Wan Yim
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Rheumatic Diseases ◽  
Pivotal Role ◽  
Human Gut ◽  
Future Role ◽  
Human Gut Microbiota ◽  
Rheumatic Manifestations

AbstractMajority of rheumatic diseases are complex and multifactorial in etiology. Emerging studies has suggested that the change of human microbiota, especially in the gut, play a pivotal role in its pathogenesis. Dysequilibrium of the gut microbiota triggers the imbalance between pro- and anti- inflammatory immune responses and results in different rheumatic manifestations, such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). In this article, current and future role of the human gut microbiota in rheumatic diseases are discussed.

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