Neuroendocrinology of the skin

Theoharides, Theoharis C.; Stewart, Julia M.; Taracanova, Alexandra; Conti, Pio; Zouboulis, Christos C.

doi:10.1007/s11154-016-9369-9

Cited by 42 publications

(40 citation statements)

References 182 publications

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“…This process is distinct from mtDNA release from damaged or dead cells in patients with sepsis that activated polymorphonuclear leucocytes through toll‐like receptors (TLR), or from or shock‐injured rat tissues . Mast cells also express TLR‐9, which can be activated by bacterial DNA sequences, leading to release of different cytokines that allow mast cells to participate in immunity against bacteria …”

Section: Discussionmentioning

confidence: 99%

“…[17] This process is distinct from mtDNA release from damaged or dead cells in patients with sepsis that activated polymorphonuclear leucocytes through toll-like receptors (TLR), [7] or from or shock-injured rat tissues. [18] Mast cells also express TLR-9, which can be activated by bacterial DNA sequences, leading to release of different cytokines [19,20] that allow mast cells to participate in immunity against bacteria. [21,22] Our findings also show that gene expression of the mitochondrial regulatory proteins UCP2, Drp1 and calcineurin is decreased in lesional psoriatic skin compared to both non-lesional and control skin.…”

Section: Discussionmentioning

confidence: 99%

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Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis

Therianou

Vasiadi

Delivanis

et al. 2019

Experimental Dermatology

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Psoriasis is characterized by keratinocyte proliferation and chronic inflammation, but the pathogenesis is still unclear. Dysregulated mitochondria (mt) could lead to reduced apoptosis and extracellular secretion of mtDNA, acting as “innate pathogen” triggering inflammation. Serum was obtained from healthy volunteers and psoriatic patients. Mitochondrial DNA was extracted from the serum and amplified with quantitative PCR (qPCR). Punch biopsies were obtained from lesional and non‐lesional psoriatic skin (10 cm apart) and from healthy volunteers, were placed in RNA later and were stored at −80°C until RNA was extracted and cDNA was synthesized; gene expression of uncoupling protein 2 (UCP2), Dynamin‐related protein 1 (Drp1) and calcineurin, involved in the regulation of mitochondria function, was detected with qPCR. Mitochondrial DNA was significantly increased (7s, P = 0.0496 and Cytochrome B, CytB, P = 0.0403) in the serum of psoriatic patients (n = 63) as compared to controls (n = 27). Gene expression was significantly reduced for UCP2 (P = 0.0218), Drp1 (P = 0.0001) and calcineurin (P = 0.0001) in lesional psoriatic skin, as compared to non‐lesional or control skin. Increased serum extracellular mtDNA in psoriatic patients and decreased expression of mitochondrial regulatory proteins in psoriatic skin suggest increased inflammation and reduced keratinocyte apoptosis, respectively. Inhibitors of mtDNA secretion and/or UCP2 stimulants may be potential treatment options.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis

Therianou

Vasiadi

Delivanis

et al. 2019

Experimental Dermatology

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“…In the brain, it functions primarily as a neurotransmitter and in the GI tract it controls gastric acid secretion and motility. However, NT is also known for its interaction with immune cells such as lymphocytes and MCs . MCs produce NT on their own .…”

Section: G‐protein‐coupled Receptors (Gpcrs)mentioning

confidence: 99%

“…However, NT is also known for its interaction with immune cells such as lymphocytes and MCs. 129 MCs produce NT on their own. 130 Soon after the discovery of NT, it was reported that MCs bind NT.…”

Section: Neuropeptide and Neurotransmitter Receptorsmentioning

confidence: 99%

Non‐IgE mediated mast cell activation

Redegeld

Kumari

et al. 2018

Immunological Reviews

159

105

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Mast cells (MCs) are innate immune cells that are scattered in tissues throughout the organism being particularly abundant at sites exposed to the environment such as the skin and mucosal surfaces. Generally known for their role in IgE-mediated allergies, they have also important functions in the maintenance of tissue integrity by constantly sensing their microenvironment for signals by inflammatory triggers that can comprise infectious agents, toxins, hormones, alarmins, metabolic states, etc. When triggered their main function is to release a whole set of inflammatory mediators, cytokines, chemokines, and lipid products. This allows them to organize the ensuing innate immune and inflammatory response in tight coordination with resident tissue cells, other rapidly recruited immune effector cells as well as the endocrine and exocrine systems of the body. To complete these tasks, MCs are endowed with a large repertoire of receptors allowing them to respond to multiple stimuli or directly interact with other cells. Here we review some of the receptors expressed on MCs (ie, receptors for Immunoglobulins, pattern recognition receptors, nuclear receptors, receptors for alarmins, and a variety of other receptors) and discuss their functional implication in the immune and inflammatory response focusing on non-IgE-mediated activation mechanisms.

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“…However, the cellular source and the triggers for the secretion of these mediators remain elusive. Increasing evidence implicates certain neuropeptides, especially corticotrophin‐releasing hormone (CRH), neurotensin (NT) and substance P (SP), as possible triggers of KC and mast cells (MC) . Moreover, such peptides and TNF have been reported to affect the expression of their own and other surface receptors.…”

Section: Introductionmentioning

confidence: 99%

TNF stimulates IL‐6, CXCL8 and VEGF secretion from human keratinocytes via activation of mTOR, inhibited by tetramethoxyluteolin

Patel

Tsilioni

Weng

et al. 2018

Experimental Dermatology

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Psoriasis is an autoimmune skin disease characterized by keratinocyte hyperproliferation and chronic inflammation. The pathogenesis of psoriasis involves proinflammatory cytokines, such as tumor necrosis factor (TNF), but the mechanism of keratinocyte activation is not well understood. Here, we show that TNF (10 or 50 ng/mL) stimulates a significant (P < .0001) gene expression and secretion of proinflammatory IL-6, CXCL8 and VEGF from both cultured human HaCaT and normal epidermal human keratinocytes (NHEKs). This effect occurs via activation of the mammalian target of rapamycin (mTOR) signalling complex as shown by Western blot analysis and phospho-ELISAs. Pretreatment with the novel natural flavonoid tetramethoxyluteolin (10-100 μmol L ) significantly (P < .0001) inhibits gene expression and secretion (P < .0001) of all 3 mediators in a concentration-dependent manner. Moreover, tetramethoxyluteolin (50 μmol L ) appears to be a potent inhibitor of the phosphorylated mTOR substrates (pmTOR , pp70S6K and p4EBP1 ) as compared to known mTOR inhibitors in keratinocytes. The present findings indicate that TNF stimulates skin inflammation via mTOR signalling. Inhibition by tetramethoxyluteolin may be used in the treatment for psoriasis.

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Neuroendocrinology of the skin

Cited by 42 publications

References 182 publications

Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis

Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis

Non‐IgE mediated mast cell activation

TNF stimulates IL‐6, CXCL8 and VEGF secretion from human keratinocytes via activation of mTOR, inhibited by tetramethoxyluteolin

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