Peroxisome Proliferator-activated Receptor-β/δ Modulates Mast Cell Phenotype

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2016 Dec 10

PMID 27935639

Citations 6

Authors

Pei-Li Yao

Jose L Morales

Frank J Gonzalez

Jeffrey M Peters

Affiliations

Soon will be listed here.

Abstract

The peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is known to have multiple anti-inflammatory effects, typically observed in endothelial cells, macrophages, T cells and B cells. Despite the fact that mast cells are important mediators of inflammation, to date, the role of PPARβ/δ in mast cells has not been examined. Hence, the present study examined the hypothesis that PPARβ/δ modulates mast cell phenotype. Bone-marrow-derived mast cells (BMMCs) and peritoneal mast cells from Pparβ/δ mice expressed higher levels of high-affinity IgE receptor (FcεRI) compared with Pparβ/δ mice. BMMCs from Pparβ/δ mice also exhibited dense granules, associated with higher expression of enzymes and proteases compared with Pparβ/δ mice. Resting BMMCs from Pparβ/δ mice secreted lower levels of inflammatory cytokines, associated with the altered activation of phospholipase Cγ1 and extracellular signal-regulated kinases compared with Pparβ/δ mice. Moreover, the production of cytokines by mast cells induced by various stimuli was highly dependent on PPARβ/δ expression. This study demonstrates that PPARβ/δ is an important regulator of mast cell phenotype.

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References

Alfredsson J, Puthalakath H, Martin H, Strasser A, Nilsson G . Proapoptotic Bcl-2 family member Bim is involved in the control of mast cell survival and is induced together with Bcl-XL upon IgE-receptor activation. Cell Death Differ. 2004; 12(2):136-44. DOI: 10.1038/sj.cdd.4401537. View

Sugiyama H, Nonaka T, Kishimoto T, Komoriya K, Tsuji K, Nakahata T . Peroxisome proliferator-activated receptors are expressed in mouse bone marrow-derived mast cells. FEBS Lett. 2000; 467(2-3):259-62. DOI: 10.1016/s0014-5793(00)01169-8. View

Pejler G, Ronnberg E, Waern I, Wernersson S . Mast cell proteases: multifaceted regulators of inflammatory disease. Blood. 2010; 115(24):4981-90. DOI: 10.1182/blood-2010-01-257287. View

Taketomi Y, Sunaga K, Tanaka S, Nakamura M, Arata S, Okuda T . Impaired mast cell maturation and degranulation and attenuated allergic responses in Ndrg1-deficient mice. J Immunol. 2007; 178(11):7042-53. DOI: 10.4049/jimmunol.178.11.7042. View

Fujimura Y, Tachibana H, Yamada K . Peroxisome proliferator-activated receptor ligands negatively regulate the expression of the high-affinity IgE receptor Fc epsilon RI in human basophilic KU812 cells. Biochem Biophys Res Commun. 2002; 297(2):193-201. DOI: 10.1016/s0006-291x(02)02139-3. View

Yao P, Chen L, Dobrzanski T, Phillips D, Zhu B, Kang B . Inhibition of testicular embryonal carcinoma cell tumorigenicity by peroxisome proliferator-activated receptor-β/δ- and retinoic acid receptor-dependent mechanisms. Oncotarget. 2015; 6(34):36319-37. PMC: 4742180. DOI: 10.18632/oncotarget.5415. View

Yao P, Morales J, Zhu B, Kang B, Gonzalez F, Peters J . Activation of peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ) inhibits human breast cancer cell line tumorigenicity. Mol Cancer Ther. 2014; 13(4):1008-17. PMC: 3981956. DOI: 10.1158/1535-7163.MCT-13-0836. View

Yao P, Chen L, Hess R, Muller R, Gonzalez F, Peters J . Peroxisome Proliferator-activated Receptor-D (PPARD) Coordinates Mouse Spermatogenesis by Modulating Extracellular Signal-regulated Kinase (ERK)-dependent Signaling. J Biol Chem. 2015; 290(38):23416-31. PMC: 4645614. DOI: 10.1074/jbc.M115.664508. View

Berent-Maoz B, Gur C, Vita F, Soranzo M, Zabucchi G, Levi-Schaffer F . Influence of FAS on murine mast cell maturation. Ann Allergy Asthma Immunol. 2011; 106(3):239-44. DOI: 10.1016/j.anai.2010.12.001. View

10.

Abraham S, St John A . Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol. 2010; 10(6):440-52. PMC: 4469150. DOI: 10.1038/nri2782. View

11.

Taketomi Y, Sugiki T, Saito T, Ishii S, Hisada M, Suzuki-Nishimura T . Identification of NDRG1 as an early inducible gene during in vitro maturation of cultured mast cells. Biochem Biophys Res Commun. 2003; 306(2):339-46. DOI: 10.1016/s0006-291x(03)00942-2. View

12.

Suzuki K, Verma I . Phosphorylation of SNAP-23 by IkappaB kinase 2 regulates mast cell degranulation. Cell. 2008; 134(3):485-95. PMC: 2586340. DOI: 10.1016/j.cell.2008.05.050. View

13.

Galli S, Borregaard N, Wynn T . Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol. 2011; 12(11):1035-44. PMC: 3412172. DOI: 10.1038/ni.2109. View

14.

Gurish M, Ghildyal N, Arm J, Austen K, Avraham S, Reynolds D . Cytokine mRNA are preferentially increased relative to secretory granule protein mRNA in mouse bone marrow-derived mast cells that have undergone IgE-mediated activation and degranulation. J Immunol. 1991; 146(5):1527-33. View

15.

Peters J, Lee S, Li W, Ward J, Gavrilova O, Everett C . Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). Mol Cell Biol. 2000; 20(14):5119-28. PMC: 85961. DOI: 10.1128/MCB.20.14.5119-5128.2000. View

16.

Jippo T, Morii E, Ito A, Kitamura Y . Effect of anatomical distribution of mast cells on their defense function against bacterial infections: demonstration using partially mast cell-deficient tg/tg mice. J Exp Med. 2003; 197(11):1417-25. PMC: 2193916. DOI: 10.1084/jem.20022157. View

17.

Ito T, Smrz D, Jung M, Bandara G, Desai A, Smrzova S . Stem cell factor programs the mast cell activation phenotype. J Immunol. 2012; 188(11):5428-37. PMC: 3358494. DOI: 10.4049/jimmunol.1103366. View

18.

Sagi-Eisenberg R, Foreman J, Shelly R . Histamine release induced by histone and phorbol ester from rat peritoneal mast cells. Eur J Pharmacol. 1985; 113(1):11-7. DOI: 10.1016/0014-2999(85)90337-1. View

19.

Sugiyama H, Nonaka T, Kishimoto T, Komoriya K, Tsuji K, Nakahata T . Peroxisome proliferator-activated receptors are expressed in human cultured mast cells: a possible role of these receptors in negative regulation of mast cell activation. Eur J Immunol. 2000; 30(12):3363-70. DOI: 10.1002/1521-4141(2000012)30:12<3363::AID-IMMU3363>3.0.CO;2-B. View

20.

Zhu B, Ferry C, Markell L, Blazanin N, Glick A, Gonzalez F . The nuclear receptor peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) promotes oncogene-induced cellular senescence through repression of endoplasmic reticulum stress. J Biol Chem. 2014; 289(29):20102-19. PMC: 4106326. DOI: 10.1074/jbc.M114.551069. View