Group V secretory PLA2 regulates TLR2-dependent eicosanoid generation in mouse mast cells through amplification of ERK and cPLA2α activation

Abstract Mast cells may be activated through Toll-like receptors (TLRs) for the dose- and time-dependent release of eicosanoids. However, the signaling mechanisms of TLR-dependent rapid eicosanoid generation are not known. We previously reported a role for group V secretory phospholipase A2 (PLA2) in regulating phagocytosis of zymosan and the ensuing eicosanoid generation in mouse resident peritoneal macrophages, suggesting a role for the enzyme in innate immunity. In the present study, we have used gene knockout mice to define an essential role for MyD88 and cytosolic PLA2α in TLR2-dependent eicosanoid generation. Furthermore, in mast cells lacking group V secretory PLA2, the time course of phosphorylation of ERK1/2 and of cPLA2α was markedly truncated, leading to attenuation of eicosanoid generation in response to stimulation through TLR2, but not through c-kit or FcεRI. These findings provide the first dissection of the mechanisms of TLR-dependent rapid eicosanoid generation, which is MyD88-dependent, requires cPLA2α, and is amplified by group V sPLA2 through its regulation of the sequential phosphorylation and activation of ERK1/2 and cPLA2α. The findings support the suggestion that group V sPLA2 regulates innate immune responses.

Download Full-text

Dual-specificity phosphatase 1: a critical regulator of innate immune responses

Biochemical Society Transactions ◽

10.1042/bst0341018 ◽

2006 ◽

Vol 34 (6) ◽

pp. 1018-1023 ◽

Cited By ~ 95

Author(s):

S.M. Abraham ◽

A.R. Clark

Keyword(s):

Innate Immunity ◽

Immune Responses ◽

P38 Mapk ◽

Time Course ◽

Inflammatory Diseases ◽

Innate Immune ◽

Mitogen Activated Protein Kinase ◽

Innate Immune Responses ◽

Inflammatory Stimuli ◽

Mitogen Activated Protein

Innate immune responses are critically dependent on MAPK (mitogen-activated protein kinase) signalling pathways, in particular JNK (c-Jun N-terminal kinase) and p38 MAPK. Both of these kinases are negatively regulated via their dephosphorylation by DUSP1 (dual-specificity phosphatase 1). Several pro- and anti-inflammatory stimuli converge to regulate the DUSP1 gene and to modulate the time course of its expression. In turn, the pattern of expression of DUSP1 dictates the kinetics of activation of JNK and p38 MAPK, and this influences the expression of several mediators of innate immunity. DUSP1 is therefore a central regulator of innate immunity, and its expression can profoundly affect the outcome of inflammatory challenges. We discuss possible implications for immune-mediated inflammatory diseases and their treatment.

Download Full-text

Parasite Recognition and Signaling Mechanisms in Innate Immune Responses to Malaria

Frontiers in Immunology ◽

10.3389/fimmu.2018.03006 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 23

Author(s):

D. Channe Gowda ◽

Xianzhu Wu

Keyword(s):

Immune Responses ◽

Innate Immune ◽

Innate Immune Responses ◽

Signaling Mechanisms

Download Full-text

Signaling Mechanisms Regulating Innate Immune Responses

Mucosal Immunology ◽

10.1016/b978-0-12-415847-4.00030-6 ◽

2015 ◽

pp. 605-622

Author(s):

Clara Abraham ◽

Stefanie N. Vogel ◽

Darren J. Perkins

Keyword(s):

Immune Responses ◽

Innate Immune ◽

Innate Immune Responses ◽

Signaling Mechanisms

Download Full-text

Zebrafish Ddx19 deficiency causes serious apoptosis and cell proliferation

10.21203/rs.2.10830/v1 ◽

2019 ◽

Author(s):

Can Shi ◽

Linzhu Bao ◽

Yao Zu ◽

Jianfeng Ren ◽

Weiming Li ◽

...

Keyword(s):

Immune Responses ◽

Cell Apoptosis ◽

Gene Knockout ◽

Innate Immune ◽

Innate Immune Responses ◽

Dead Box ◽

Body Development ◽

Small Head ◽

Pericardial Edema ◽

Knockout Technology

Abstract Background: DDX19 is known as for its role in mRNA transport. It is also involved in translation and innate immune responses. However, the function of Ddx19 during body development rarely reported. We know that ddx19 plays an important role in development of organisms, but we don't understand how it affects the process of cell development. Results: Here, we report ddx19-deleted mutation in zebrafish, obtained two types with base deletion of 46 bp and 7 bp using CRISPR/Cas9 gene knockout technology, show morphologic defects such as small head, small eyes, pericardial edema and trunk curvature in 24 hours post fertilization (hpf). The maximum survival time of ddx19 -/- was less than 5 day post fertilization (dpf). In comparison to the wildtype, the mutant embryos showed widespread up-regulation of cell apoptosis, and significant decrease in the number of cells. Conclusions: These data indicate loss of ddx19 is lethal, and is associated with cell apoptosis and proliferation abnormalities in the organism. Our results reveal that ddx19 is essential for the development of zebrafish embryos, which deepens the understanding of the developmental function of DEAD-box genes family.

Download Full-text

Oral Immune Activation by Disgust and Disease-Related Pictures

Journal of Psychophysiology ◽

10.1027/0269-8803/a000143 ◽

2015 ◽

Vol 29 (3) ◽

pp. 119-129 ◽

Cited By ~ 4

Author(s):

Richard J. Stevenson ◽

Deborah Hodgson ◽

Megan J. Oaten ◽

Luba Sominsky ◽

Mehmet Mahmut ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Innate Immune Response ◽

Negative Control ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Markers ◽

Before And After ◽

Secondary Analyses ◽

Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

Download Full-text