Activation of Microglia by Histamine and Substance P

Zhu, Jin; Qu, Chen; Lü, Xiang; Zhang, Shu

doi:10.1159/000363041

Cited by 73 publications

(55 citation statements)

References 55 publications

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“…In addition, the same laboratory reported similar results in a second paper, comparing the effects of histamine and substance P on mitochondrial membrane depolarization as well as on the production of TNF-a-, IL-6-and reactive oxygen species (ROS) of primary rat microglial cells (Zhu et al, 2014). The data suggest that histamine causes H 1 R-and H 4 R-dependent stimulation of TNF-a, IL-6 and ROS release.…”

Section: Non-neuronal Cells Of the Brainmentioning

confidence: 53%

“…The data suggest that histamine causes H 1 R-and H 4 R-dependent stimulation of TNF-a, IL-6 and ROS release. Interestingly, while histamine caused mitochondrial depolarization, substance P was ineffective with regard to this parameter (Zhu et al, 2014).…”

Section: Non-neuronal Cells Of the Brainmentioning

confidence: 97%

“…However, these results need further confirmation, specifically because none of the animal-or cell line-based studies discussed in this section (Karlstedt et al, 2013;Ferreira et al, 2012;Dong et al, 2014;Zhu et al, 2014) included H 4 R-deficient negative controls (e.g. siRNA knockdown in cellular models or knockout animals).…”

Section: Non-neuronal Cells Of the Brainmentioning

confidence: 98%

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The histamine H4-receptor and the central and peripheral nervous system: A critical analysis of the literature

Schneider

Seifert

2016

Neuropharmacology

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Section: Non-neuronal Cells Of the Brainmentioning

confidence: 53%

Section: Non-neuronal Cells Of the Brainmentioning

confidence: 97%

Section: Non-neuronal Cells Of the Brainmentioning

confidence: 98%

See 1 more Smart Citation

The histamine H4-receptor and the central and peripheral nervous system: A critical analysis of the literature

Schneider

Seifert

2016

Neuropharmacology

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“…This finding also raises the question of whether we are missing important therapeutic avenues by studying microglia and MCs in isolation [19]. Our previous study showed that the neuromediators histamine and SP triggered microglial activation, indicating the possibility of communication between MCs and microglia [25]. However, direct evidence concerning whether MCs could affect microglial activation was lacking.…”

Section: Discussionmentioning

confidence: 99%

Induction of Microglial Activation by Mediators Released from Mast Cells

Zhang¹,

Wang²,

Dong³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Microglia are the resident immune cells in the brain and play a pivotal role in immune surveillance in the central nervous system (CNS). Brain mast cells are activated in CNS disorders and induce the release of several mediators. Thus, brain mast cells, rather than microglia, are the “first responders” due to injury. However, the functional aspects of mast cell-microglia interactions remain uninvestigated. Methods: Conditioned medium from activated HMC-1 cells induces microglial activation similar to co-culture of microglia with HMC-1 cells. Primary cultured microglia were examined by flow cytometry analysis and confocal microscopy. TNF- alpha and IL-6 were measured with commercial ELISA kits. Cell signalling was analysed by Western blotting. Results: In the present study, we found that the conditioned medium from activated HMC-1 cells stimulated microglial activation and the subsequent production of the pro-inflammatory factors TNF-α and IL-6. Co-culture of microglia and HMC-1 cells with corticotropin-releasing hormone (CRH) for 24, 48 and 72 hours increased TNF-α and IL-6 production. Antagonists of histamine receptor 1 (H₁R), H₄R, proteinase-activated receptor 2 (PAR2) or Toll-like receptor 4 (TLR4) reduced HMC-1-induced pro-inflammatory factor production and MAPK and PI3K/AKT pathway activation. Conclusions: These results imply that activated mast cells trigger microglial activation. Interactions between mast cells and microglia could constitute a new and unique therapeutic target for CNS inflammation-related diseases.

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“…Histamine induces release of pro-inflammatory factors such as tumor necrosis factor-α and interleukin-6 (IL-6) from activated microglia, via H1R and H4 receptor-MAPK and PI3K/AKT-NF-kappa B signaling pathway [14]. Moreover, it induces the production of reactive oxygen species (ROS) [15]. Histamine also acts as a nitric-oxideregulating factor by stimulating inducible nitric oxide synthase expression in microglia from neonatal rat brain [16].…”

Section: Introductionmentioning

confidence: 99%

Clemastine Confers Neuroprotection and Induces an Anti-Inflammatory Phenotype in SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

et al. 2014

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Mutations in the Cu(2+)/Zn(2+) superoxide dismutase 1 (SOD1) gene underlie 14-23 % of familial and 1-7 % of sporadic cases of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease characterized by a specific loss of motor neurons in the brain and spinal cord. Neuroinflammation and oxidative stress are emerging as key players in the pathogenesis of ALS, thus justifying the interest in glial cells and particularly microglia, in addition to motor neurons, as novel therapeutic approaches against ALS. Recently, histamine was proven to participate in the pathogenesis of neuroinflammatory and neurodegenerative diseases, and particularly, microglia was shown to be sensitive to the histamine challenge mainly through histamine H1 receptors. Clemastine is a first-generation and CNS-penetrant H1 receptor antagonist considered as a safe antihistamine compound that was shown to possess immune suppressive properties. In order to investigate if clemastine might find promising application in the treatment of ALS, in this work, we tested its action in the SOD1(G93A) mouse model which is extensively used in ALS preclinical studies. We demonstrated that chronic clemastine administration in SOD1(G93A) mice reduces microgliosis, modulates microglia-related inflammatory genes, and enhances motor neuron survival. Moreover, in vitro, clemastine is able to modify several activation parameters of SOD1(G93A) microglia, and particularly CD68 and arginase-1 expression, as well as phospho-ERK1/2 and NADPH oxidase 2 levels. Being clemastine a drug already employed in clinical practice, our results strongly encourage its further exploitation as a candidate for preclinical trials and a new modulator of neuroinflammation in ALS.

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Activation of Microglia by Histamine and Substance P

Cited by 73 publications

References 55 publications

The histamine H4-receptor and the central and peripheral nervous system: A critical analysis of the literature

The histamine H4-receptor and the central and peripheral nervous system: A critical analysis of the literature

Induction of Microglial Activation by Mediators Released from Mast Cells

Clemastine Confers Neuroprotection and Induces an Anti-Inflammatory Phenotype in SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

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