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Reduction of GPSM3 expression akin to the arthritis-protective SNP rs204989 differentially affects migration in a neutrophil model

Genes & Immunity volume 17, pages 321–327 (2016)Cite this article

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Abstract

G Protein Signaling Modulator-3 (GPSM3) is a leukocyte-specific regulator of G protein-coupled receptors (GPCRs), which binds inactivated Gαi·GDP subunits and precludes their reassociation with Gβγ subunits. GPSM3 deficiency protects mice from inflammatory arthritis and, in humans, GPSM3 single-nucleotide polymorphisms (SNPs) are inversely associated with the risk of rheumatoid arthritis development; recently, these polymorphisms were linked to one particular SNP (rs204989) that decreases GPSM3 transcript abundance. However, the precise role of GPSM3 in leukocyte biology is unknown. Here, we show that GPSM3 is induced in the human promyelocytic leukemia NB4 cell line following retinoic acid treatment, which differentiates this cell line into a model of neutrophil physiology (NB4*). Reducing GPSM3 expression in NB4* cells, akin to the effect ascribed to the rs204989 C>T transition, disrupts cellular migration toward leukotriene B4 (LTB4) and (to a lesser extent) interleukin-8 (a.k.a. IL-8 or CXCL8), but not migration toward formylated peptides (fMLP). As the chemoattractants LTB4 and CXCL8 are involved in recruitment of neutrophils to the arthritic joint, our results suggest that the arthritis-protective GPSM3 SNP rs204989 may act to decrease neutrophil chemoattractant responsiveness.

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Acknowledgements

We thank Dr Sherman Weissman for his generous gift of the NB4 cell line at the onset of these studies. This work was supported in part by the National Institutes of Health under Award Number U54GM104942.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA

    B J Gall, A B Schroer, J D Gross, V Setola & D P Siderovski

  2. Department of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine, Morgantown, WV, USA

    V Setola

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Correspondence to D P Siderovski.

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Gall, B., Schroer, A., Gross, J. et al. Reduction of GPSM3 expression akin to the arthritis-protective SNP rs204989 differentially affects migration in a neutrophil model. Genes Immun 17, 321–327 (2016). https://doi.org/10.1038/gene.2016.26

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