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Int. J. Mol. Sci. 2015, 16(1), 2252-2268; doi:10.3390/ijms16012252

Inhibition of the IgE-Mediated Activation of RBL-2H3 Cells by TIPP, a Novel Thymic Immunosuppressive Pentapeptide

1
Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
2
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
3
National Glycoengineering Research Center, Shandong University, Jinan 250012, China
*
Author to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 12 November 2014 / Accepted: 12 January 2015 / Published: 20 January 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

TIPP is a novel thymic immunosuppressive pentapeptide originally obtained from calf thymic immunosuppressive extract. The present study aimed to investigate the inhibitory activity of TIPP on IgE-mediated activation of RBL-2H3 cells. Release of β-hexosaminidase and histamine, intracellular calcium, membrane ruffling, mRNA levels of cytokines, cyclooxygenase-2 (COX-2) expression, and activation of mitogen-activated protein kinases (MAP kinases) and NF-κB were determined by colorimetric assay, fluorescence spectrophotometer, confocal fluorescence microscope, quantification PCR, and Western blot, respectively. The results showed that TIPP significantly inhibited the degranulation in IgE-antigen complex-stimulated RBL-2H3 cells without cytotoxicity. TIPP significantly suppressed the increase of intracellular calcium and the rearrangement of F-actin, attenuated the transcription of pro-inflammatory cytokines (IL-3, -4, -6, -13, TNF-α, and monocyte chemotactic protein-1 (MCP-1)), and decreased the expression of COX-2. Western blot analysis showed that TIPP had an inhibitory activity on the phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and ERK kinase 1/2 (MEK1/2), and inhibited the activation of NF-κB. The data suggested that TIPP effectively suppressed IgE-mediated activation of RBL-2H3 cells via blocking MEK/ERK and NF-κB signaling pathways. View Full-Text
Keywords: allergy; IgE; RBL-2H3 cell; MAP kinases; NF-κB; TIPP allergy; IgE; RBL-2H3 cell; MAP kinases; NF-κB; TIPP
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lian, Q.; Cheng, Y.; Zhong, C.; Wang, F. Inhibition of the IgE-Mediated Activation of RBL-2H3 Cells by TIPP, a Novel Thymic Immunosuppressive Pentapeptide. Int. J. Mol. Sci. 2015, 16, 2252-2268.

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