EMAIL THIS PAGE TO A FRIEND

Journal of immunology (Baltimore, Md. : 1950)

IL-3 Maintains Activation of the p90S6K/RPS6 Pathway and Increases Translation in Human Eosinophils.


PMID 26276876

Abstract

IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines, such as IL-5, IL-3, and GM-CSF, are typically present in atopic diseases, including allergic asthma. As a result of the functional redundancy of these three cytokines on eosinophils and the loss of IL-5R on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these three cytokines signal through a common β-chain receptor but yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce the production of proteins, such as semaphorin-7A, without affecting mRNA levels suggests a unique influence of IL-3 on translation. The purpose of this study was to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared with IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF, or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein S6 (RPS6) and the upstream kinase 90-kDa ribosomal S6 kinase (p90S6K). Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared with circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations identify IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB1409242
Anti-IL3 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB1400138
Anti-IL3 antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
SAB4300484
Anti-RPS6 (Ab-235) antibody produced in rabbit, affinity isolated antibody
SAB1300250
Anti-RPS6 (N-term) antibody produced in rabbit, Ig fraction of antiserum, buffered aqueous solution
HPA031153
Anti-RPS6 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2107629
Anti-RPS6 antibody produced in rabbit, affinity isolated antibody
SAB4300407
Anti-RPS6KA1 (Ab-348) antibody produced in rabbit, affinity isolated antibody
SAB4300408
Anti-RPS6KA1 (Ab-352) antibody produced in rabbit, affinity isolated antibody
HPA007981
Anti-RPS6KA1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
R5145 Anti-Rsk1 antibody produced in rabbit, whole antiserum
SAB4501211
Anti-RSK1 antibody produced in rabbit, affinity isolated antibody
HPA042273
Anti-SEMA7A antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB4700529 Monoclonal Anti-CD108 antibody produced in mouse, clone MEM-150, purified immunoglobulin, buffered aqueous solution
WH0006194M1
Monoclonal Anti-RPS6 antibody produced in mouse, clone 3H1-F2, purified immunoglobulin, buffered aqueous solution
WH0006195M1
Monoclonal Anti-RPS6KA1 antibody produced in mouse, clone 2E3, purified immunoglobulin, buffered aqueous solution
SAB1404334
Monoclonal Anti-RPS6KA1 antibody produced in mouse, clone 4E11, purified immunoglobulin, buffered aqueous solution
SAB5300384
Monoclonal Anti-RPS6KA1 antibody produced in mouse, clone 10B1D7A9, ascites fluid
WH0008482M1
Monoclonal Anti-SEMA7A antibody produced in mouse, clone 3D3, purified immunoglobulin, buffered aqueous solution
SAB1404584
Monoclonal Anti-SEMA7A antibody produced in mouse, clone 1G1, purified immunoglobulin, buffered aqueous solution