scholarly journals The Detrimental and Beneficial Functions of Macrophages After Cochlear Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuan Zhang ◽  
Yiyuan Li ◽  
Xiaolong Fu ◽  
Pengjun Wang ◽  
Qin Wang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Spiral Ganglion ◽  
Morphological Characteristics ◽  
Acoustic Trauma ◽  
Spiral Ganglion Neuron ◽  
Exact Role ◽  
Pathological Conditions ◽  
Age Related ◽  
Ototoxic Drug

Macrophages are the main intrinsic immune cells in the cochlea; they can be activated and play a complicated role after cochlear injury. Many studies have shown that the number of macrophages and their morphological characteristics within the major cochlear partitions undergo significant changes under various pathological conditions including acoustic trauma, ototoxic drug treatment, age-related cochlear degeneration, selective hair cell (HC) and spiral ganglion neuron (SGN) elimination, and surgery. However, the exact role of these macrophages after cochlear injury is still unclear. Regulating the migration and activity of macrophages may be a therapeutic approach to reduce the risk or magnitude of trauma-induced hearing loss, and this review highlights the role of macrophages on the peripheral auditory structures of the cochlea and elucidate the mechanisms of macrophage injury and the strategies to reduce the injury by regulating macrophage.

scholarly journals Role of Leptin in the Activation of Immune Cells

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Patricia Fernández-Riejos ◽  
Souad Najib ◽  
Jose Santos-Alvarez ◽  
Consuelo Martín-Romero ◽  
Antonio Pérez-Pérez ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Energy Homeostasis ◽  
Humoral Factors ◽  
Endocrine Organ ◽  
Pathological Conditions ◽  
Immune Mediated ◽  
Infection Susceptibility

Adipose tissue is an active endocrine organ that secretes various humoral factors (adipokines), and its shift to production of proinflammatory cytokines in obesity likely contributes to the low-level systemic inflammation that may be present in metabolic syndrome-associated chronic pathologies such as atherosclerosis. Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. One of these functions is the connection between nutritional status and immune competence. The adipocyte-derived hormone leptin has been shown to regulate the immune response, innate and adaptive response, both in normal and pathological conditions. The role of leptin in regulating immune response has been assessed in vitro as well as in clinical studies. It has been shown that conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders such as autoimmune diseases are associated with increased secretion of leptin and production of proinflammatory pathogenic cytokines. Thus, leptin is a mediator of the inflammatory response.

The Role of Immune Cells in the Brain during Physiological and Pathological Conditions

2015 ◽  
Vol 45 (5) ◽  
pp. 232-239 ◽  
Author(s):  
Tina C. Franklin ◽  
Eric S. Wohleb ◽  
Ronald S. Duman
Keyword(s):  
Immune Cells ◽  
Pathological Conditions ◽  
The Brain

scholarly journals Altered Ca2+ Homeostasis in Immune Cells during Aging: Role of Ion Channels

2020 ◽  
Vol 22 (1) ◽  
pp. 110
Author(s):  
Dorina Zöphel ◽  
Chantal Hof ◽  
Annette Lis
Keyword(s):  
Immune Cells ◽  
Irreversible Process ◽  
Cell Function ◽  
Immune Cell ◽  
Compensatory Mechanisms ◽  
Cellular Environment ◽  
Age Related ◽  
Dependent Processes ◽  
Equal Density

Aging is an unstoppable process and begins shortly after birth. Each cell of the organism is affected by the irreversible process, not only with equal density but also at varying ages and with different speed. Therefore, aging can also be understood as an adaptation to a continually changing cellular environment. One of these very prominent changes in age affects Ca2+ signaling. Especially immune cells highly rely on Ca2+-dependent processes and a strictly regulated Ca2+ homeostasis. The intricate patterns of impaired immune cell function may represent a deficit or compensatory mechanisms. Besides, altered immune function through Ca2+ signaling can profoundly affect the development of age-related disease. This review attempts to summarize changes in Ca2+ signaling due to channels and receptors in T cells and beyond in the context of aging.

scholarly journals Solving the Puzzle: What Is the Role of Progestogens in Neovascularization?

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1686
Author(s):  
Zhi Xia ◽  
Jian Xiao ◽  
Qiong Chen
Keyword(s):  
Progesterone Receptor ◽  
Sex Steroids ◽  
Underlying Mechanism ◽  
Physiological Changes ◽  
Exact Role ◽  
The Past ◽  
Naturally Occurring ◽  
Pathological Conditions ◽  
Insight Into

Ovarian sex steroids can modulate new vessel formation and development, and the clarification of the underlying mechanism will provide insight into neovascularization-related physiological changes and pathological conditions. Unlike estrogen, which mainly promotes neovascularization through activating classic post-receptor signaling pathways, progesterone (P4) regulates a variety of downstream factors with angiogenic or antiangiogenic effects, exerting various influences on neovascularization. Furthermore, diverse progestins, the synthetic progesterone receptor (PR) agonists structurally related to P4, have been used in numerous studies, which could contribute to unequal actions. As a result, there have been many conflicting observations in the past, making it difficult for researchers to define the exact role of progestogens (PR agonists including naturally occurring P4 and synthetic progestins). This review summarizes available evidence for progestogen-mediated neovascularization under physiological and pathological circumstances, and attempts to elaborate their functional characteristics and regulatory patterns from a comprehensive perspective.

scholarly journals PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Yanzhuo Zhang ◽  
Zhe Lv ◽  
Yudong Liu ◽  
Huan Cao ◽  
Jianwang Yang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
Cell Senescence ◽  
Prolyl Isomerase ◽  
Age Related ◽  
Pin1 Protein

A growing amount of evidence has confirmed the crucial role of the prolyl isomerase PIN1 in aging and age-related diseases. However, the mechanism of PIN1 in age-related hearing loss (ARHL) remains unclear. Pathologically, ARHL is primarily due to the loss and dysfunction of hair cells (HCs) and spiral ganglion cells (SGCs) in the cochlea. Therefore, in this study, we aimed to investigate the role of PIN1 in protecting hair cells and auditory HEI-OC1 cells from senescence. Enzyme-linked immunosorbent assays, immunohistochemistry, and immunofluorescence were used to detect the PIN1 protein level in the serum of ARHL patients and C57BL/6 mice in different groups, and in the SGCs and HCs of young and aged C57BL/6 mice. In addition, a model of HEI-OC1 cell senescence induced by H2O2 was used. Adult C57BL/6 mice were treated with juglone, or juglone and NAC, for 4 weeks. Interestingly, we found that the PIN1 protein expression decreased in the serum of patients with ARHL, in senescent HEI-OC1 cells, and in the cochlea of aged mice. Moreover, under H2O2 and juglone treatment, a large amount of ROS was produced, and phosphorylation of p53 was induced. Importantly, PIN1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-α. Overexpression of PIN1 reversed the increased level of p-p53 and rescued HEI-OC1 cells from senescence. Furthermore, PIN1 mediated cellular senescence by the PI3K/Akt/mTOR signaling pathway. In vivo data from C57BL/6 mice showed that treatment with juglone led to hearing loss. Taken together, these findings demonstrated that PIN1 may act as a vital modulator in hair cell and HEI-OC1 cell senescence.

scholarly journals The role of glucocorticoids for spiral ganglion neuron survival

2009 ◽  
Vol 1277 ◽  
pp. 3-11 ◽  
Author(s):  
David Xu Jin ◽  
Zhaoyu Lin ◽  
Debin Lei ◽  
Jianxin Bao
Keyword(s):  
Spiral Ganglion ◽  
Ganglion Neuron ◽  
Spiral Ganglion Neuron ◽  
Neuron Survival

scholarly journals Innate Immunity to Spiral Ganglion Neuron Loss: A Neuroprotective Role of Fractalkine Signaling in Injured Cochlea

2021 ◽  
Vol 15 ◽  
Author(s):  
Andrew Rigel Stothert ◽  
Tejbeer Kaur
Keyword(s):  
Innate Immunity ◽  
Nervous System ◽  
Immune System ◽  
Inner Ear ◽  
Immune Cells ◽  
Spiral Ganglion ◽  
Sensory Cells ◽  
Specific Chemical ◽  
Ganglion Neurons

Immune system dysregulation is increasingly being attributed to the development of a multitude of neurodegenerative diseases. This, in large part, is due to the delicate relationship that exists between neurons in the central nervous system (CNS) and peripheral nervous system (PNS), and the resident immune cells that aid in homeostasis and immune surveillance within a tissue. Classically, the inner ear was thought to be immune privileged due to the presence of a blood-labyrinth barrier. However, it is now well-established that both vestibular and auditory end organs in the inner ear contain a resident (local) population of macrophages which are the phagocytic cells of the innate-immune system. Upon cochlear sterile injury or infection, there is robust activation of these resident macrophages and a predominant increase in the numbers of macrophages as well as other types of leukocytes. Despite this, the source, nature, fate, and functions of these immune cells during cochlear physiology and pathology remains unclear. Migration of local macrophages and infiltration of bone-marrow-derived peripheral blood macrophages into the damaged cochlea occur through various signaling cascades, mediated by the release of specific chemical signals from damaged sensory and non-sensory cells of the cochlea. One such signaling pathway is CX3CL1-CX3CR1, or fractalkine (FKN) signaling, a direct line of communication between macrophages and sensory inner hair cells (IHCs) and spiral ganglion neurons (SGNs) of the cochlea. Despite the known importance of this neuron-immune axis in CNS function and pathology, until recently it was not clear whether this signaling axis played a role in macrophage chemotaxis and SGN survival following cochlear injury. In this review, we will explore the importance of innate immunity in neurodegenerative disease development, specifically focusing on the regulation of the CX3CL1-CX3CR1 axis, and present evidence for a role of FKN signaling in cochlear neuroprotection.

scholarly journals Polymerization of misfolded Z alpha-1antitrypin protein lowers CX3CR1 expression in human PBMCs

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Srinu Tumpara ◽  
Matthias Ballmaier ◽  
Sabine Wrenger ◽  
Mandy König ◽  
Matthias Lehmann ◽  
...  
Keyword(s):  
Immune Cells ◽  
Amyloid Fibrils ◽  
Tissue Homeostasis ◽  
Misfolded Proteins ◽  
Human Pbmcs ◽  
Pathological Conditions ◽  
Alpha 1 Antitrypsin ◽  
Specific Ligand ◽  
Cx3cr1 Expression

The CX3CR1 (chemokine (C-X3-C motif) receptor 1) expression levels on immune cells have significant importance in maintaining tissue homeostasis under physiological and pathological conditions. The factors implicated in the regulation of CX3CR1 and its specific ligand CX3CL1 (fractalkine) expression remain largely unknown. Recent studies provide evidence that host`s misfolded proteins occurring in the forms of polymers or amyloid fibrils can regulate CX3CR1 expression. Herein, a novel example demonstrates that polymers of human ZZ alpha-1 antitrypsin (Z-AAT) protein, resulting from its conformational misfolding due to the Z (Glu342Lys) mutation in SERPINA1 gene, strongly lower CX3CR1 mRNA expression in human PBMCs. This parallels with increase of intracellular levels of CX3CR1 and Z-AAT proteins. Presented data indicate the involvement of the CX3CR1 pathway in the Z-AAT-related disorders and further support the role of misfolded proteins in CX3CR1 regulation.

scholarly journals Polymerization of misfolded protein lowers CX3CR1 expression in human PBMCs

2020 ◽  
Author(s):  
Srinu Tumpara ◽  
Matthias Ballmaier ◽  
Sabine Wrenger ◽  
Mandy König ◽  
Matthias Lehmann ◽  
...  
Keyword(s):  
Immune Cells ◽  
Amyloid Fibrils ◽  
Misfolded Proteins ◽  
Human Pbmcs ◽  
Extracellular Polymers ◽  
Pathological Conditions ◽  
Alpha1 Antitrypsin ◽  
Specific Ligand ◽  
Cx3cr1 Expression

AbstractThe CX3CR1 (chemokine (C-X3-C motif) receptor 1) expression levels on immune cells have significant importance in maintaining tissue homeostasis under physiological and pathological conditions. The factors implicated in the regulation of CX3CR1 and its specific ligand CX3CL1 (fractalkine) expression remain largely unknown. Recent studies provide evidence that host‘s misfolded proteins occurring in the forms of polymers or amyloid fibrils can regulate CX3CR1 expression. Herein, we present a novel example that polymers of human ZZ alpha1-antitrypsin (Z-AAT) protein, resulting from its conformational misfolding due to the Z (Glu342Lys) mutation in SERPINA1 gene, strongly lower CX3CR1 expression in human PBMCs. We also show that extracellular polymers of Z-AAT are internalized by PBMCs, which parallels with increased intracellular levels of CX3CR1 protein. Our findings support the role of extracellular misfolded proteins in CX3CR1 regulation and encourage conducting further studies on this issue.

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