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Journal of Immunology Research
Volume 2018 (2018), Article ID 5201759, 9 pages
https://doi.org/10.1155/2018/5201759
Review Article

The Role of Phospholipase C Signaling in Macrophage-Mediated Inflammatory Response

1College of Veterinary Medicine and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 48 Wenhui East Road, Yangzhou, Jiangsu 225009, China
2Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA
3College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450002, China

Correspondence should be addressed to Clinton Jones; ude.etatsko@01senoj.tnilc and Gaiping Zhang; moc.361@3002gnipiaggnahz

Received 24 June 2017; Revised 6 October 2017; Accepted 5 November 2017; Published 8 February 2018

Academic Editor: Zissis Chroneos

Copyright © 2018 Liqian Zhu et al. 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.

Abstract

Macrophages are crucial members of the mononuclear phagocyte system essential to protect the host from invading pathogens and are central to the inflammatory response with their ability to acquire specialized phenotypes of inflammatory (M1) and anti-inflammatory (M2) and to produce a pool of inflammatory mediators. Equipped with a broad range of receptors, such as Toll-like receptor 4 (TLR4), CD14, and Fc gamma receptors (FcγRs), macrophages can efficiently recognize and phagocytize invading pathogens and secrete cytokines by triggering various secondary signaling pathways. Phospholipase C (PLC) is a family of enzymes that hydrolyze phospholipids, the most significant of which is phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Cleavage at the internal phosphate ester generates two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), both of which mediate in diverse cellular functions including the inflammatory response. Recent studies have shown that some PLC isoforms are involved in multiple stages in TLR4-, CD14-, and FcγRs-mediated activation of nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and interferon regulatory factors (IRFs), all of which are associated with the regulation of the inflammatory response. Therefore, secondary signaling by PLC is implicated in the pathogenesis of numerous inflammatory diseases. This review provides an overview of our current knowledge on how PLC signaling regulates the macrophage-mediated inflammatory response.