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Histamine Induces Microglia Activation and the Release of Proinflammatory Mediators in Rat Brain Via H1R or H4R. 2020

Wei Zhang, and Xiaojun Zhang, and Yan Zhang, and Chen Qu, and Xiqiao Zhou, and Shu Zhang
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.

Histamine is a major peripheral inflammatory mediator and a neurotransmitter in the central nervous system. We have reported that histamine induces microglia activation and releases proinflammatory factors in primary cultured microglia. Whether histamine has similar effects in vivo is unknown. In the present study, we aimed to investigate the role of histamine and its receptors in the release of inflammatory mediators and activation of microglia in rat brain. We site-directed injected histamine, histamine receptor agonists or histamine receptor antagonists in the rat lateral ventricle using stereotaxic techniques. Flow cytometry was employed to determine histamine receptor expression in rat microglia. Microglia activation was assessed by Iba1 immunohistochemistry. The levels of tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-10 (IL-10) were measured with commercial enzyme-linked immunosorbent assay (ELISA) kits, TNF-α, IL-1β and IL-10 mRNA expressions were determined with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). We found that all four types of histamine receptors were expressed in rat brain microglia. Histamine was able to induce microglia activation and subsequent production of the inflammatory factors TNF-α, IL-1β and IL-10, and these effects were partially abolished by H1R and H4R antagonists. However, H2R and H3R antagonists significantly increased production of TNF-α and IL-1β, and decreased IL-10 levels. The H1R or H4R agonists stimulated the production of TNF-α and IL-1β, while the H2R or H3R agonists increased IL-10 release. Our results demonstrate that histamine induces microglia activation and the release of both proinflammatory and anti-inflammatory factors in rat brain, thus contributing to the development of inflammation in the brain. Graphical Abstract Histamine induces microglia activation and the release of both proinflammatory (TNF-α and IL-1β) and anti-inflammatory factors (IL-10) in rat brain, thus contributing to the development of inflammation in the brain.

UI MeSH Term Description Entries
D008297 Male Males
D011969 Receptors, Histamine H1 A class of histamine receptors discriminated by their pharmacology and mode of action. Most histamine H1 receptors operate through the inositol phosphate/diacylglycerol second messenger system. Among the many responses mediated by these receptors are smooth muscle contraction, increased vascular permeability, hormone release, and cerebral glyconeogenesis. (From Biochem Soc Trans 1992 Feb;20(1):122-5) H1 Receptor,Histamine H1 Receptors,H1 Receptors,Histamine H1 Receptor,Receptors, H1,H1 Receptor, Histamine,H1 Receptors, Histamine,Receptor, H1,Receptor, Histamine H1
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D006632 Histamine An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin
D006634 Histamine H1 Antagonists Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood. Antihistamines, Classical,Antihistaminics, Classical,Antihistaminics, H1,Histamine H1 Antagonist,Histamine H1 Receptor Antagonist,Histamine H1 Receptor Antagonists,Histamine H1 Receptor Blockaders,Antagonists, Histamine H1,Antagonists, Histamine H1 Receptor,Antihistamines, Sedating,Blockaders, Histamine H1 Receptor,First Generation H1 Antagonists,H1 Receptor Blockaders,Histamine H1 Blockers,Receptor Blockaders, H1,Antagonist, Histamine H1,Classical Antihistamines,Classical Antihistaminics,H1 Antagonist, Histamine,H1 Antagonists, Histamine,H1 Antihistaminics,Sedating Antihistamines
D000074040 Receptors, Histamine H4 G-Protein-coupled histamine receptors that are expressed primarily in BONE MARROW as well as in peripheral tissues and organs. They are expressed by immune cells that include EOSINOPHILS; T-CELLS; DENDRITIC CELLS; and MAST CELLS. H4 Receptors,Histamine H4 Receptor,Histamine H4 Receptors,H4 Receptor, Histamine,H4 Receptors, Histamine,Receptor, Histamine H4,Receptors, H4
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017628 Microglia The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. Microglial Cell,Cell, Microglial,Microglial Cells,Microglias
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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