Dataset Information

Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcepsilonRI-aggregation reveals a complex network of genes involved in inflammatory responses.

ABSTRACT: Mast cells are well established effectors of IgE-triggered allergic reactions and immune responses to parasitic infections. Recent studies indicate that mast cells may play roles in adaptive and innate immunity, suggesting an innovative view of the regulation of immune responses. Here, we profiled the transcriptome of human mast cells sensitized with IgE alone, or stimulated by FcepsilonRI aggregation.Our data show that among 8,793 genes examined, 559 genes are differentially regulated in stimulated mast cells when compared with resting/unstimulated mast cells. The major functional categories of upregulated genes include cytokines, chemokines, and other genes involved in innate and adaptive immune-responses. We observed the increased expression of over 63 gene-transcripts following IgE-sensitization alone. Our data was validated using Real-Time-PCR; ELISA and western blot. We confirmed that IgE alone does not trigger mast cell-immediate responses, such as calcium signals, degranulation or protein-phosphorylation.This report represents a substantial advance in our understanding of the genome wide effects triggered by "passive sensitization" or active stimulation of human mast cells, supporting mast cells' potential involvement in a wide range of inflammatory responses.

SUBMITTER: Jayapal M

PROVIDER: S-EPMC1564015 | biostudies-literature | 2006 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcepsilonRI-aggregation reveals a complex network of genes involved in inflammatory responses.

Jayapal Manikandan M Tay Hwee Kee HK Reghunathan Renji R Zhi Liang L Chow Kah Kiong KK Rauff Mary M Melendez Alirio J AJ

BMC genomics 20060816

<h4>Background</h4>Mast cells are well established effectors of IgE-triggered allergic reactions and immune responses to parasitic infections. Recent studies indicate that mast cells may play roles in adaptive and innate immunity, suggesting an innovative view of the regulation of immune responses. Here, we profiled the transcriptome of human mast cells sensitized with IgE alone, or stimulated by FcepsilonRI aggregation.<h4>Results</h4>Our data show that among 8,793 genes examined, 559 genes are ...[more]

PMID: 16911805

Similar Datasets

Project description:BackgroundEfficient development of atopic diseases requires interactions between allergen and adjuvant to initiate and amplify the underlying inflammatory responses. Substance P (SP) and hemokinin-1 (HK-1) are neuropeptides that signal through the neurokinin-1 receptor (NK1R) to promote inflammation. Mast cells initiate the symptoms and tissue effects of atopic disorders, secreting TNF and IL-6 after FcεRI cross-linking by antigen-IgE complexes (FcεRI-activated mast cells [FcεRI-MCs]). Additionally, MCs express the NK1R, suggesting an adjuvant role for NK1R agonists in FcεRI-MC-mediated pathologies; however, in-depth research addressing this relevant aspect of MC biology is lacking.ObjectiveWe sought to investigate the effect of NK1R signaling and the individual roles of SP and HK-1 as potential adjuvants for FcεRI-MC-mediated allergic disorders.MethodsBone marrow-derived mast cells (BMMCs) from C57BL/6 wild-type (WT) or NK1R(-/-) mice were used to investigate the effects of NK1R signaling on FcεRI-MCs. BMMCs generated from Tac1(-/-) mice or after culture with Tac4 small interfering RNA were used to address the adjuvancy of SP and HK-1. WT, NK1R(-/-), and c-Kit(W-sh/W-sh) mice reconstituted with WT or NK1R(-/-) BMMCs were used to evaluate NK1R signaling on FcεRI-MC-mediated passive local and systemic anaphylaxis and on airway inflammation.ResultsFcεRI-activated MCs upregulated NK1R and HK-1 transcripts and protein synthesis, without modifying SP expression. In a positive signaling loop HK-1 promoted TNF and IL-6 secretion by MC degranulation and protein synthesis, the latter through the phosphoinositide 3-kinase/Akt/nuclear factor κB pathways. In vivo NK1R signaling was necessary for the development of passive local and systemic anaphylaxis and airway inflammation.ConclusionsFcεRI stimulation of MCs promotes autocrine secretion of HK-1, which signals through NK1R to provide adjuvancy for efficient development of FcεRI-MC-mediated disorders.

Dataset Information

Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcepsilonRI-aggregation reveals a complex network of genes involved in inflammatory responses.

Publications

Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcepsilonRI-aggregation reveals a complex network of genes involved in inflammatory responses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets